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HUMAN  METABOLISM  WITH  ENEMATA 
OF  ALCOHOL,  DEXTROSE, 

AND  LEVULOSE 


THORNE  M.  CARPENTER 


TIE  mum  Of  THE 

MAR  1  9  1826 
mmmw  of  slunqis 


Published  by  the  Carnegie  Institution  of  Washington 

Washington,  December  1925 


CARNEGIE  INSTITUTION  OF  WASHINGTON 

Publication  No.  369 


RUMFORD  PRESS 
CONCORD 


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PREFACE. 

The  researches  which  are  given  in  this  monograph  were  carried  out 
during  the  years  1915  to  1917,  and  in  their  conduct  I  was  greatly  assisted 
by  a  number  of  individuals.  I  wish  to  express  my  appreciation  of  the 
cooperation  and  the  willingness  of  the  four  medical  students  who  underwent 
this  unusual  form  of  study  of  metabolism.  The  determinations  of  the 
alcohol  in  urine  and  wash-outs  were  all  made  by  Miss  E.  B.  Babcock,  whose 
mastery  of  the  Nicloux  method  rendered  it  possible  to  supplement  the 
studies  of  the  respiratory  exchange.  The  analyses  of  expired  air  and  of  the 
excreta  were  carried  out  for  the  most  part  by  Mr.  F.  J.  Murray  and  Mr. 
I.  B.  Simon,  and  they  also  assisted  in  the  measurements  of  the  respiratory 
exchange.  It  is  a  pleasure  to  acknowledge  the  great  improvement  in  the 
manuscript  as  the  result  of  the  very  careful  editorial  revision  bv  Miss  A.  N. 
Darling.1 

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Nutrition  Laboratory  of  the 
Carnegie  Institution  of  Washington, 

Boston,  Massachusetts,  December  15,  1924. 

*Died  Jan.  25,  1925. 


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CONTENTS. 


PAGE 

Introduction .  1 

Previous  researches  on  rectal  alimentation .  2 

Researches  with  rectal  introduction  of  dextrose .  3 

Researches  with  rectal  introduction  of  levulose .  20 

Researches  with  rectal  introduction  of  alcohol .  20 

General  summary  of  literature  on  rectal  alimentation . •  21 

Plan  and  methods  of  study  with  rectal  feeding  of  alcohol  and  sugars .  22 

Determination  of  amount  of  absorption .  23 

Determinations  in  study  of  urine .  24 

Determination  of  respiratory  exchange .  24 

Analysis  of  expired  air .  24 

Method  of  recording  respiration-rate  and  activity .  25 

Method  of  recording  pulse-rate .  25 

Apparatus  for  detecting  sleep . .  25 

Routine  of  observations  of  respiratory  exchange .  26 

Absorption  of  alcohol  when  introduced  into  the  rectum .  27 

Absorption  with  a  5  per  cent  alcohol  solution .  27 

Absorption  with  a  7.5  per  cent  alcohol  solution .  29 

Absorption  with  a  10  per  cent  alcohol  solution .  30 

Absorption  of  dextrose  when  introduced  into  the  rectum .  30 

Absorption  of  levulose  when  introduced  into  the  rectum .  34 

Studies  of  urine  eliminated .  37 

Elimination  and  concentration  of  alcohol  in  urine  after  rectal  injection  (long  col¬ 
lection  periods) .  37 

Urine  with  rectal  injections  of  a  5  per  cent  alcohol  solution .  38 

Summary  of  results  with  rectal  injections  of  a  5  per  cent  alcohol  solution  40 

Urine  with  rectal  injections  of  a  7.5  per  cent  alcohol  solution .  40 

Summary  of  results  with  rectal  injections  of  a  7.5  per  cent  alcohol 

solution . 43 

Urine  with  rectal  injections  of  a  10  per  cent  alcohol  solution .  43 

Comparison  observations  of  alcohol  in  urine  after  its  ingestion  by  mouth .  43 

Elimination  and  concentration  of  alcohol  in  urine  after  its  rectal  injection  (short 

collection  periods) .  45 

Comparison  experiments  with  urine  collected  at  short  intervals  after  ingestion  of 

alcohol  solutions  by  mouth .  52 

Discussion  of  results  obtained  with  short  periods  of  urine  collection .  52 

Effect  of  coffee  drinking  on  elimination  of  a  reducing  substance .  58 

Conjugated  alcohol .  58 

Effect  of  rectal  injections  upon  volume  of  urine  and  elimination  of  nitrogen  and 

sodium  chloride .  59 

Effect  on  urine  of  rectal  introduction  of  a  solution  of  sodium  chloride .  60 

Effect  on  urine  of  rectal  introduction  of  a  5  per  cent  solution  of  alcohol .  62 

Effect  on  urine  of  rectal  introduction  of  a  7.5  per  cent  solution  of  alcohol .  64 

Effect  on  urine  of  rectal  introduction  of  a  10  per  cent  solution  of  alcohol ...  66 

Effect  on  urine  of  rectal  introduction  of  a  dextrose  solution .  66 

Effect  on  urine  of  rectal  introduction  of  a  solution  of  levulose .  69 

Percentile  changes  in  urinary  volume,  and  in  elimination  of  nitrogen  and  of 

sodium  chloride  as  affected  by  rectal  injection .  72 

Percentile  changes  in  volume  of  urine .  74 

Percentile  changes  in  nitrogen  elimination .  76 

Percentile  changes  in  elimination  of  sodium  chloride .  78 

Percentile  changes  in  ratio  of  nitrogen  to  sodium  chloride .  79 

Summary  of  percentile  changes  with  rectal  injection .  79 


v 


VI 


CONTENTS. 


PAGE 

Respiratory  exchange  with  rectal  injection .  80 

Respiratory  exchange  with  rectal  injection  of  a  solution  of  sodium  chloride .  83 

Sodium-chloride  experiments  with  gasometer  method .  83 

Results  of  measurements  before  rectal  injection .  87 

Results  of  measurements  after  rectal  injection  of  sodium  chloride .  93 

General  conclusions  and  discussion  of  composite  chart .  96 

Sodium-chloride  experiments  with  clinical  respiration  chamber .  97 

General  conclusions  regarding  experiments  with  clinical  respiration 

chamber .  103 

Respiratory  exchange  with  rectal  injection  of  alcohol  solutions .  103 

Experiments  with  a  5  per  cent  alcohol  solution .  103 

Results  of  measurements  before  rectal  injection . .  104 

Results  of  measurements  after  rectal  injection  of  a  5  per  cent  alcohol 

solution .  108 

Discussion  of  composite  chart .  112 

General  conclusions  regarding  experiments  with  a  5  per  cent  alcohol 

solution .  113 

Experiments  with  a  7.5  per  cent  alcohol  solution .  114 

Observations  with  gasometer  and  mask  method .  114 

Results  of  measurements  before  rectal  injection .  114 

Results  of  measurements  after  rectal  injection  of  a  7.5  per  cent 

alcohol  solution .  116 

Discussion  of  composite  chart  and  general  conclusions . .  118 

Observations  with  clinical  respiration  chamber .  120 

Discussion  of  composite  chart  of  chamber  experiments .  126 

General  summary  of  results  with  a  7.5  per  cent  alcohol  solution .  127 

Experiments  with  a  10  per  cent  alcohol  solution .  128 

Results  of  measurements  before  rectal  injection .  128 

Results  of  measurements  after  rectal  injection  of  a  10  per  cent  alcohol 

solution .  129 

Discussion  of  composite  chart  of  experiments  with  a  10  per  cent  alcohol 

solution .  131 

Respiratory  exchange  as  influenced  by  alcohol  given  by  mouth .  132 

Results  of  measurements  before  alcohol  was  taken .  134 

Results  of  measurements  after  alcohol  was  taken .  136 

Discussion  of  composite  chart  for  mouth  experiments .  137 

General  conclusions  regarding  experiments  with  ingestion  of  alcohol  by  mouth  139 

Respiratory  exchange  with  rectal  injection  of  dextrose .  140 

Results  of  measurements  before  rectal  injection .  143 

Results  of  measurements  after  rectal  injection  of  dextrose  (gasometer  method)  146 
Results  of  measurements  after  rectal  injection  of  dextrose  (chamber  method)  149 

Discussion  of  composite  chart .  149 

General  conclusions  regarding  respiratory  exchange  with  rectal  introduction 

of  dextrose .  150 

Respiratory  exchange  with  rectal  injection  of  levulose . . .  150 

Results  of  measurements  before  rectal  injection .  151 

Results  of  measurements  after  rectal  injection  of  levulose .  155 

Discussion  of  composite  chart,  and  conclusions .  156 

Respiratory  exchange  with  oral  ingestion  of  sugars .  157 

General  discussion  of  results .  159 

Practical  considerations .  159 

Temperature  of  material  injected .  159 

Rate  of  flow .  160 

Volume  of  injection .  161 

Maximum  time  of  retention .  161 

Position  of  subject  during  injection .  162 

Use  of  sodium  chloride .  162 

Addition  of  opium .  163 

Removal  of  unabsorbed  material .  163 


CONTENTS.  Vll 

PAGE 

General  discussion  of  results — Continued. 

Subjective  impressions  regarding  the  various  solutions . .  164 

Sodium-chloride  solutions.  .  .  . . 164 

Alcohol  solutions .  165 

Sugar  solutions .  165 

General  summary  of  impressions .  166 

Theoretical  considerations .  166 

Utilization  of  alcohol  in  rectal  feeding .  166 

Absorption  of  alcohol  as  an  indication  of  utilization .  166 

Excretion  of  alcohol  in  urine  as  a  measure  of  utilization .  167 

Utilization  of  alcohol  in  rectal  feeding  as  indicated  by  the  respiratory  ex¬ 
change .  175 

Utilization  of  dextrose  when  introduced  rec tally .  185 

Utilization  of  levulose  with  rectal  introduction .  187 

Hypothetical  discussion .  189 

Hypothesis  regarding  the  metabolism  with  rectal  feeding .  192 

Summary .  194 


• 

■ 


. 


I 


HUMAN  METABOLISM  WITH  ENEMATA  OF 
ALCOHOL,  DEXTROSE,  AND  LEVULOSE 


BY 

THORNE  M.  CARPENTER 


With  ninety-one  text-figures. 


v/ 


»• 


. 


HUMAN  METABOLISM  WITH  ENEMATA  OF 
ALCOHOL,  DEXTROSE,  AND  LEVULOSE. 


By  Thorne  M.  Carpenter. 


INTRODUCTION. 

The  ingestion  of  food,  drink,  and  medicine  is  usually  by  way  of  the  mouth. 
The  material  then  passes  through  the  alimentary  tract  where  it  is  prepared, 
if  necessary,  for  absorption  into  the  blood-stream,  or  else  carried  entirely 
through  the  alimentary  canal  and  rejected  unchanged.  Under  certain 
conditions,  the  taking  of  material  by  mouth  is  not  feasible  and,  indeed,  is 
well  nigh  impossible.  Such  conditions  are  coma,  unconsciousness,  inability 
or  unwillingness  of  the  individual  to  cooperate  (as  in  insanity),  congenital 
or  accidental  obstruction  of  the  alimentary  canal,  and  during  or  after 
anesthesia.  The  material  must  then  be  introduced  in  some  other  manner, 
the  various  paths  used  being  intravenous,  intramuscular,  intraperitoneal, 
and  rectal  injection. 

Rectal  injections  of  saline  and  glucose  solutions  in  operative  procedures 
are  common,  but  these  are  in  most  cases  empirical.  Attempts  have  been 
made  to  introduce  rectally  many  substances,  but  there  is  a  great  deal  of 
confusion  of  ideas  and,  in  much  of  the  experimental  work,  lack  of  uniformity 
in  results,  as  to  the  metabolic  utility  of  rectal  injection.  Undoubtedly  much 
of  the  earlier  work  on  rectal  feeding,  particularly  with  reference  to  protein, 
is  of  little  value,  because  of  the  lack  of  knowledge  as  to  how  or  in  what  form 
the  food  material  was  absorbed.  There  is  thus  need  for  a  thorough,  scien¬ 
tific  study  of  the  metabolism  when  nutrient  material  is  injected  by  rectum. 
The  results  of  such  study  should  be  of  immediate  value  to  clinicians  and 
nutrition  experts  who  are  obliged  to  resort  to  this  method. 

Aside  from  its  practical  application,  there  is  another  way  in  which  such  a 
study  is  of  value.  Rectal  introduction  is  an  unusual  and  abnormal  method 
of  making  nutritive  material  available.  It  is  conceivable  that  the  path  or 
paths  in  the  animal  body  through  which  the  substance  is  carried  may  be 
different  from  those  when  it  is  ingested  by  mouth;  consequently  the  steps 
in  the  cleavage  of  the  material  may  be  different  in  speed  and  character  from 
those  when  food  is  taken  by  mouth.  The  method  of  studying  the  metab¬ 
olism  by  the  introduction  of  substances  in  various  ways  may  be  considered 
as  a  differential,  topographic,  or  regional  method,  which  conceivably  would 
give  results  of  value  in  the  interpretation  of  physiological  and  biochemical 
processes. 

In  1913,  the  Nutrition  Laboratory  published  a  program,1  tentatively 
proposed,  for  an  investigation  of  the  physiological  action  of  ethyl  alcohol 

1  Benedict  and  Dodge:  Tentative  plan  for  a  proposed  investigation  into  the  physiological  action 
of  ethyl  alcohol  in  man.  Proposed  correlative  study  of  the  psychological  effects  of  alcohol  on 
man.  Privately  printed,  Boston,  Massachusetts,  1913.  See,  also,  Dodge  and  Benedict, 
Carnegie  Inst.  Wash.  Pub.  No.  232,  1915,  pp.  266-275. 


1 


2 


HUMAN  METABOLISM  WITH  ENEMATA. 


in  man.  One  of  the  methods  of  ingestion  suggested  in  the  program  was 
that  of  rectal  enema,  either  of  alcohol  alone  or  with  glucose  solutions.  The 
experimental  results  reported  in  the  present  monograph  are  the  outcome  of 
a  study  of  the  physiological  effect  of  alcohol  when  introduced  in  this  manner. 

It  was  originally  intended  in  this  research  to  investigate  only  the  effect  of 
alcohol  upon  the  respiratory  exchange,  with  particular  reference  to  the 
absorption  of  the  alcohol  and  to  the  change  in  respiratory  quotient  as  an 
indication  of  the  actual  utilization  of  alcohol  in  the  metabolism.  The  study 
subsequently  led  to  the  determination  of  the  amount,  composition,  and 
alcohol-content  of  the  urine.  During  the  course  of  the  experiments,  observa¬ 
tions  were  also  made  upon  the  effect  of  the  injection  of  dextrose  and  levulose 
solutions. 

The  research  began  in  1915  and  was  carried  out  with  four  medical  students. 
In  the  spring  of  1917,  two  of  these  students  entered  military  service  and  the 
other  two  were  likewise  no  longer  available,  so  that  it  was  not  feasible  to 
continue  the  study  with  these  men.  Preliminary  reports  1  of  several  phases 
of  the  investigation  have  been  made,  and  a  brief  summary  of  results  of  a 
special  group  of  experiments  with  rectal  injection  of  a  solution  containing 
7.5  per  cent  of  alcohol  by  weight  was  given  by  Miles 2  in  a  recent  monograph. 

PREVIOUS  RESEARCHES  ON  RECTAL  ALIMENTATION. 

The  rectal  introduction  of  food  and  medicaments  is  very  old  historically. 
Bensaude  and  Vicente3  review  the  history  of  the  use  of  bile  in  medicine, 
stating  that  Egyptian  papyrus  thirteen  centuries  before  Christ  gave  pre¬ 
scriptions  for  enemas.  The  writings  of  Hippocrates,  5» 6*  8«  Galen,  4» 5*  6»  8» 
and  Celsus  4>  5* 6*  7*  8»  mention  the  possibilities  of  nutrition  by  way  of  the 
rectum.  The  consensus  of  opinion  in  the  literature  is  that  modern  scientific 
investigation  of  the  utility  of  rectal  injection  began  with  the  investigation 
of  Voit  and  Bauer  in  1869. 9  Their  work,  however,  was  not  concerned  with 
the  materials  used  in  the  research  reported  here  and  is  of  historical  interest 

°nly. 

In  the  following  section  a  review  is  given  of  the  most  important  investiga¬ 
tions  upon  rectal  feeding  with  man  and  animals,  with  special  reference  to 
the  introduction  of  alcohol,  dextrose,  and  levulose.  This  review  of  the 
literature  includes  not  only  those  researches  in  which  studies  were  made  of 
absorption  or  of  respiratory  exchange,  but  also  such  other  researches  as  may 
assist  in  the  interpretation  of  the  results  obtained  from  the  series  presented 
in  this  report. 

1  Carpenter  and  Babcock:  Journ.  Biol.  Chem.,  1917,  29,  Proc.  Am.  Soc.  Biol.  Chem.,  p.  xxviii; 

Carpenter,  Am.  Journ.  Physiol.,  1917,  42,  p.  605;  Ibid.,  1922,  59,  p.  440. 

2  Miles:  Carnegie  Inst.  Wash.  Pub.  No.  333, 1924,  p.  111. 

3  Bensaude  and  Vicente:  Bull,  et  mem.  Soc.  med.  d.  hopitaux  de  Paris,  1919,  43,  p.  932. 

4  Schoenborn:  Zur  Frage  der  Resorption  von  Kohlehydraten  im  menschlichen  Rectum.  Diss., 

Wurzburg,  1897. 

6  Bial:  Ausnutzung  von  Pepton-  und  Pepton-Alkohol-Klysmen.  Diss.,  Halle,  1903. 

6  Zehmisch:  Ausnutzung  von  Nahrklystieren.  Diss.,  Halle,  1903. 

7  Wendt:  Ueber  Anwendung,  Indicationen  und  Erfolge  der  Ernahrung  per  Rectum.  Diss., 

Jena,  1896. 

8  Plantenga:  Der  Werth  der  Nahrklystiere.  Diss.,  Freiburg,  1898. 

9  Voit  and  Bauer:  Zeitschr.  f.  Biol.,  1869,  5,  p.  536. 


PREVIOUS  RESEARCHES  ON  RECTAL  ALIMENTATION. 


3 


RESEARCHES  WITH  RECTAL  INTRODUCTION  OF  DEXTROSE. 

The  studies  on  the  rectal  introduction  of  dextrose,  which  are  much  more 
numerous  than  those  with  the  other  two  materials,  are  first  considered  in 
chronological  sequence. 

Eichorst,  1871. — An  extensive  investigation  upon  the  absorption  of  va¬ 
rious  food  materials  in  the  large  intestine  was  carried  out  by  Eichorst1  with 
a  dog  as  subject.  In  studying  the  absorption  of  milk  sugar,  Eichorst  found 
an  elimination  of  sugar  in  the  urine.  These  results  led  to  further  studies  on 
the  absorption  of  sugar  in  which  he  employed  honey.  This  was  diluted  and 
given  to  the  dog  by  injection;  the  dog  was  fed  a  mixed  diet  at  the  same  time. 
As  the  experimenter  did  not  find  so  much  sugar  in  the  urine  as  he  expected, 
he  analyzed  the  feces  and  obtained  sugar.  The  experiment  continued  6 
days.  On  the  first  day  he  gave  1  gram  of  honey  and  found  in  the  urine  €.3 
gram  sugar  and  in  the  feces  0.6  gram.  The  amount  given  was  gradually 
increased  each  day  until,  on  the  sixth  day,  the  dog  was  receiving  16  grams. 
On  that  day  he  found  3.4  grams  of  sugar  in  the  urine  and  3.3  grams  in  the 
feces. 

Schoenborn,  1897. — One  of  the  most  extensive  researches  on  the  absorp¬ 
tion  of  dextrose  was  carried  out  by  Schoenborn.2  His  investigations  consisted 
of  10  experiments  with  10  patients,  with  the  quantity  of  sugar  injected  rang¬ 
ing  from  25.0  grams  to  174  grams;  the  time  of  retention  varied  from  1  hour 
to  29  hours.  With  25  grams,  the  amount  unabsorbed  was  from  3.5  grams 
to  15  grams;  with  34  grams,  the  maximum  amount  unabsorbed  was  9.2 
grams. 

At  first  he  injected  the  solutions  without  using  a  previous  cleansing  enema, 
but  later  he  gave  an  enema  of  500  c.  c.  of  water  before  the  injection  and  the 
same  amount  for  the  final  enema  or  wash-out.  The  quantity  obtained 
from  the  final  wash-out  varied.  To  insure  the  entire  removal  of  the  sugar 
from  the  intestines  by  the  wash-out,  he  occasionally  used  additional  enemas, 
but  reports  that  sugar  was  never  found  in  the  material  obtained  from  the 
second.  When  the  sugar  w^as  given  in  the  ordinary  way,  i.  e.,  by  mouth, 
it  was  in  no  instance  eliminated  in  the  urine.  With  the  largest  quantity 
(174  grams),  only  30  grams  were  found  to  be  unabsorbed,  leaving  144  grams 
as  the  actual  absorption  in  1  hour.  Schoenborn  believes  that  1  to  2  hours 
is  sufficiently  long  for  the  retention  of  the  injection,  as  the  maximum  ab¬ 
sorption  occurred  in  the  first  hour. 

Experiments  were  made  in  which  special  precautions  were  taken  to  pre¬ 
vent  the  sugar  solution  from  passing  into  the  portal  system.  For  this  pur¬ 
pose  he  introduced  a  dilatable  bag  into  the  upper  part  of  the  rectum.  He 
found  its  introduction  very  difficult,  but  was  successful  in  the  third  attempt. 
The  balloon  was  introduced  by  means  of  a  pair  of  tongs  to  about  10  cm. 
above  the  rectal  opening.  He  then  injected  into  the  lower  part  of  the  rec¬ 
tum  150  c.  c.  of  a  12  per  cent  sugar  solution  (about  18  grams  of  sugar). 
After  the  retention  of  the  solution  for  1  hour,  the  intestine  was  washed  out 
and  the  urine  sampled  every  2  hours.  The  cleansing  enema  was  given  at 

11  o’clock,  but  the  resulting  fluid  was  sugar-free,  as  was  also  the  urine  at 

12  and  2  o’clock.  At  4  o’clock  there  was  sufficient  sugar  to  determine  (0.35 
gram),  and  in  the  urine  at  6  and  8  o’clock,  there  was  still  a  reducing  sub¬ 
stance.  The  night  urine  was  again  sugar-free.  He  concluded  that  the 
sugar  was  absorbed  through  the  middle  hemorrhoidal  vein.  Thus  it  had 

1  Eichorst:  Arch.  f.  d.  ges.  Physiol.,  1871,  4,  p.  570. 

2  Schoenborn:  Zur  Frage  der  Resorption  von  Kohlehydraten  ira  menschlichen  Rectum.  Diss., 

Wurzburg,  1897. 


4 


HUMAN  METABOLISM  WITH  ENEMATA. 


avoided  glycogen  formation  in  the  liver,  and  a  part  was  eliminated  through 
the  urine. 

Schoenborn  also  had  an  opportunity  to  carry  out  additional  experiments 
with  a  patient  in  the  hospital,  from  whom  10  cm.  of  the  lower  end  of  the  rec¬ 
tum  had  been  removed.  With  this  subject  the  balloon  was  inserted  to  a 
point  10  cm.  higher  than  the  new  opening.  A  quantity  of  sugar  solution 
with  a  low  concentration  was  injected  in  the  portion  of  the  rectum  below 
the  balloon.  The  solution  was  retained  for  1  hour  and  the  urine  sampled 
every  2  hours.  No  glycosuria  appeared.  The  author’s  long  series  of  results 
varied  as  to  the  absorption  of  the  sugar  introduced  into  the  rectum,  but  on 
the  whole  they  indicate  a  large  absorption  of  glucose  solution. 

Strauss,  1897. — Strauss1  was  particularly  interested  in  glycosuria  after 
the  injection  of  dextrose  and  milk  sugar  by  rectum.  He  made  experiments 
on  4  patients  with  whom  the  ingestion  of  100  grams  of  dextrose  by  mouth 
showed  a  good  tolerance.  From  20  to  50  grams  in  a  10  per  cent  solution 
were  given  the  patient  in  the  morning.  A  number  of  experiments  were  also 
carried  out  in  which  larger  amounts  were  given  rectally  in  20  per  cent  solu¬ 
tions,  the  largest  being  100  grams  in  500  c.  c.  of  water.  In  some  cases  the 
enemas  were  retained  only  1  or  2  hours;  in  other  cases  they  were  rejected 
after  2  or  3  hours.  The  urines  were  collected  for  several  periods  of  13^> 
hours  each.  In  no  case  was  sugar  found  in  the  urine.  In  another  series  of 
experiments,  the  sugar  was  given  in  the  evening  and  the  urine  collected  for 
two  2-hour  periods,  and  then  for  the  remainder  of  the  night.  In  these  ob¬ 
servations,  also,  no  sugar  was  eliminated  in  the  urine.  To  4  patients  with 
whom  100  grams  of  dextrose  taken  orally  produced  glycosuria,  he  gave  100 
grams  of  dextrose  in  500  c.  c.  of  water  by  rectum,  the  material  being  retained 
45  minutes  to  1  hour;  no  sugar  was  found  in  the  urine.  No  details  are  given 
as  to  the  amount  actually  absorbed  in  these  experiments. 

von  Leube,  1897. — In  a  general  discussion  of  the  value  of  rectal  feeding  and 
the  materials  to  be  used,  von  Leube  2  reports  two  experiments.  In  one,  70 
grams  of  dextrose  were  given  in  300  c.  c.  of  water  and  retained  for  5^£  hours 
in  the  rectum.  The  spontaneous  stools  were  analyzed  and  it  was  found 
that  63.8  grams  of  the  dextrose  were  absorbed.  In  the  other  experiment, 
50  grams  were  given  in  300  c.  c.  of  water  and  retained  for  12  hours,  with  an 
absorption  of  46  grams,  von  Leube  recommends  a  volume  of  not  over  300 
c.  c.  and  concentrations  of  10  to  20  per  cent.  He  discusses  the  possibility  of 
absorption  by  the  lower  and  middle  hemorrhoidal  veins  only,  which  would 
lead  to  glycosuria,  but  says  that  this  never  has  occurred,  so  he  believes  that 
the  injection  goes  into  the  colon  and  large  intestine  in  such  a  way  that  the 
blood  of  the  superior  hemorrhoidal  vein  carries  it  to  the  portal  circulation. 
He  admits  the  possibility  of  fermentation,  but  believes  that  the  difficulty  is 
more  theoretical  than  practical,  as  the  major  portion  of  the  absorption  takes 
place  in  the  first  hour,  and  this  is  too  short  a  time  for  the  entire  amount  to 
disappear  by  way  of  putrefaction. 

Muller,  1897. — The  purpose  of  a  study  made  by  J.  Muller 3  was  to  determine 
whether  acetone  was  formed  in  the  digestive  tract  or  in  some  other  portion 
of  the  body.  By  use  of  a  meat-fat  diet,  the  subjects  were  brought  to  a  con¬ 
dition  in  which  acetone  was  eliminated  in  the  urine  and  breath.  After  sev¬ 
eral  days  he  tried  intravenous  injection  of  dextrose,  but  as  tests  on  himself 
did  not  give  good  reactions,  he  decided  to  discontinue  the  use  of  this  method 
of  injection.  He  then  resorted  to  rectal  injection,  giving  88  to  110  grams  in 
volumes  from  600  to  700  c.  c.  At  first  he  allowed  the  enema  to  remain  5  to  7 


1  Strauss:  Charite-Annalen,  1897,  22,  p.  264. 

2  von  Leube:  Leyden’s  Handbuch  der  Ernahrungstherapie  u.  Diatetik.  Leipsic,  1897,  1,  p.  496. 

3  Mtlller:  Verhandl.  d.  Kongr.  f.  inn.  Med.,  1898,  p.  454. 


PREVIOUS  RESEARCHES  ON  RECTAL  ALIMENTATION. 


5 


hours,  but  later  only  2  hours,  as  he  believed  this  was  sufficient  time  for 
good  absorption  (about  50  per  cent).  He  never  found  sugar  in  the  urine. 
After  2  days  of  rectal  injection  of  carbohydrate,  he  gave  carbohydrate  by 
mouth  on  2  days  in  the  form  of  rye  bread. 

There  were  three  series  of  experiments.  In  the  first,  the  average  elimina¬ 
tion  of  acetone  in  4  days  on  a  meat-fat  diet  was  197  mg.  per  24  hours.  He 
then  injected  rectally  56  grams  and  50  grams  of  dextrose  on  2  days.  The 
average  elimination  of  acetone  for  the  2  days  was  387  mg.  On  each  of  the 
next  2  days,  50  grams  of  carbohydrate  by  mouth  were  given,  with  an  average 
elimination  of  127  mg. 

In  the  second  series  the  carbohydrate-free  diet  was  taken  for  11  days, 
with  a  mean  average  for  the  acetone  eliminated  by  mouth  and  in  the  urine 
of  472  mg.;  3  days  followed  on  which  43,  60,  and  65  grams  of  dextrose  were 
given  by  rectum,  with  a  subsequent  three  days  on  which  40, 40,  and  50  grams 
of  carbohydrate  were  given  by  mouth.  The  average  elimination  of  acetone 
with  rectal  injection  was  468  mg.  and  with  oral  ingestion  212  mg.  In  the 
third  series,  on  5  days  of  a  carbohydrate-free  diet,  the  average  elimination 
of  acetone  was  333  mg.  With  3  days  of  dextrose  injection  (68,  62,  and  58 
grams),  the  average  acetone  elimination  was  434  mg.,  and  with  2  days  of 
oral  ingestion  (45  and  30  grams),  the  elimination  was  267  mg. 

Muller  concludes  that  carbohydrate  prevents  the  formation  of  acetone 
only  when  it  passes  through  the  gastro-intestinal  canal  in  a  normal  manner, 
that  is,  if  carbohydrate  enters  the  body  by  another  way  it  is  without  in¬ 
fluence.  Then  he  draws  the  remarkable  conclusion  that  the  source  of  ace¬ 
tone  formation  must  be  in  the  intestinal  canal. 

Schuman-Leclerq,  1901. — In  an  extensive  study  on  the  influence  of  food 
upon  the  acetone  excretion  with  himself  as  subject,  Schuman-Leclerq1 
used  dextrose  and  levulose  by  rectum.  For  13  days  he  had  a  mixed  diet 
and  then  for  25  days  he  took  by  mouth  from  500  to  1,966  grams  of  meat, 
usually  1,000  grams.  On  a  number  of  these  meat  days  sugar  was  added  to 
the  diet,  being  taken  by  mouth  or  by  rectum.  The  urine  was  collected  in 
24-hour  periods  and  the  acetone  determined.  There  were  5  days  with  25  to 
50  grams  of  dextrose  by  mouth,  2  days  with  50  and  100  grams  of  dextrose  by 
rectum,  followed  by  4  days  of  meat  diet  only,  and  again  with  50  grams  of 
dextrose  by  rectum;  another  day  with  25  grams  of  dextrose  by  rectum,  and 
later  3  days  with  50,  75,  and  100  grams  of  levulose  by  rectum. 

The  data  do  not  indicate  positively  in  all  cases  that  the  carbohydrate 
taken  by  rectum  lowered  the  acetone  excretion,  but  there  is  a  tendency 
toward  lower  values  on  the  days  on  which  carbohydrate  was  taken  or  on  the 
day  following;  the  nitrogen  excretion  in  the  urine  was  materially  lower  on 
many  of  the  days  on  which  the  carbohydrate  was  taken  rectally. 

Bergmark2  has  criticized  these  experiments,  saying  that  the  acetone 
elimination  was  so  variable  that  no  conclusions  can  be  drawn  regarding  the 
effect  of  rectal  feeding  of  carbohydrate  upon  the  acetone  excretion. 

Reach ,  1 902. — Reach 3  studied  the  respiratory  exchange  after  oral  inges¬ 
tion  of  several  sugars,  including  dextrose,  and  compared  it  with  the  respir¬ 
atory  exchange  when  the  same  material  was  injected  by  rectum.  The 
experiments  were  carried  out  on  a  27-year  old  man  who  was  a  patient  in 
the  hospital.  His  height  was  152  cm.  and  weight  49  kg.  The  respiratory 
exchange  was  measured  by  means  of  the  Zuntz-Geppert  apparatus,  and  all 
experiments  were  with  the  subject  in  the  post-absorptive  condition. 

The  basal  value  was  first  obtained  in  one  or  two  periods  of  observation. 

1  Schuman-Leclerq:  Wiener  klin.  Wochenschr.,  1901,  p.  237. 

2  Bergmark:  Skand.  Arch.  f.  Physiol.,  1915,  32,  p.  362 

3  Reach:  Arch.  f.  exp.  Path,  u  Pharm.,  1902  47,  p.  231. 


6 


HUMAN  METABOLISM  WITH  ENEMATA. 


These  periods  were  usually  of  short  duration.  Four  experiments  were  made 
in  which  the  respiratory  exchange  was  measured  for  several  hours  without 
the  ingestion  of  sugar.  In  general,  there  was  slight,  if  any,  alteration  in  the 
respiratory  quotient,  the  tendency  being  towards  a  fall.  The  total  oxygen 
consumption  likewise  showed  no  material  changes,  although  at  times  there 
were  wide  variations.  The  ingestion  by  mouth  of  60  grams  of  dextrose  in 
120  to  200  c.  c.  of  water  raised  the  respiratory  quotient  from  0.79  to  0.87  in 
less  than  2  hours  after  ingestion.  In  another  case,  it  raised  the  quotient 
from  0.72  to  0.82  in  about  2  hours.  When  the  sugar  was  given  by  rectum, 
in  one  experiment  the  respiratory  quotient  before  injection  was  0.81,  and 
2  to  2}/%  hours  afterwards  the  quotient  was  0.84.  In  another  observation, 
the  quotient  before  the  injection  was  0.86,  but  fell  to  0.80;  after  the  injection 
of  sugar  it  rose  to  0.88  and  0.87  in  a  little  over  2  hours.  In  the  third  ex¬ 
periment,  there  was  no  rise  in  the  respiratory  quotient.  The  author  con¬ 
cludes  that  there  is  a  slight  absorption  of  dextrose  by  rectum,  although  it  is 
not  so  rapid  and  complete  as  when  given  by  mouth.  Glycosuria  did  not 
occur  in  any  case. 

In  addition  to  the  respiration  experiments,  he  studied  the  fermentation  of 
the  sugar  solution  by  determinations  made  on  the  feces.  The  feces  were 
moistened  with  water  and  a  similar  quantity  of  a  6  per  cent  solution  of  sugar 
was  mixed  with  them.  An  aliquot  of  this  was  filtered  and  diluted  10  times 
and  the  sugar  determined  in  the  filtrate.  Then  a  second  quantity  of  like 
size  was  incubated,  and  after  3  hours  the  sugar  was  determined  in  the  same 
way.  In  the  first  case  the  feces  were  obtained  from  a  patient  with  diarrhea, 
and  16  per  cent  of  the  material  disappeared;  in  the  second  case  the  individ¬ 
ual  was  in  ordinary  health,  and  5  per  cent  disappeared.  Reach  also  made 
2  experiments  with  the  feces  of  a  dog  in  which  the  material  that  disappeared 
amounted  to  0  and  2  per  cent,  respectively.  He  believes  that  the  absorp¬ 
tion  of  carbohydrate  can  not  be  determined  with  accuracy  from  the  amount 
remaining  in  the  stools  because  of  the  possibility  of  decomposition  in  the 
intestine. 

Deucher,  1903. — One  experiment  with  a  patient  is  reported  by  Deucher,1 
in  which  5  portions  of  dextrose,  each  of  40  grams  in  500  c.  c.  of  water,  were 
given  by  rectum  on  one  day,  or  200  grams  of  sugar  in  all.  To  3  portions  10 
drops  of  tincture  of  opium  were  added  and  to  another  30  drops  of  tincture  of 
opium.  The  absorption  of  the  individual  enemas  varied  from  72  to  85  per 
cent;  the  total  absorption  during  19  hours  was  155  grams,  or  77  per  cent  of 
the  sugar  given.  The  next  day  he  gave  3  injections,  each  of  30  grams  of  dex¬ 
trose  in  300  c.  c.  of  water.  No  stool  was  passed  until  the  following  day;  no 
sugar  was  found  in  either  the  feces  or  the  urine. 

Zehmisch,  1903. — In  giving  the  results  of  a  2-day  experiment  on  himself, 
Zehmisch2  points  out  that  most  of  the  previous  work  in  rectal  feeding  has 
been  done  with  single  food  materials  and  not  on  a  combination,  and  it  was  his 
purpose  to  determine  how  much  of  a  mixed  enema  could  be  absorbed  by  the 
rectum  and  colon.  For  the  injection  he  prepared  an  emulsion  made  of  14 
eggs,  1,400  c.  c.  of  milk,  140  grams  of  dextrose,  and  7  grams  of  salt.  This  was 
made  up  to  a  volume  of  2,040  c.  c.  Six  portions,  each  of  about  250  c.  c., 
were  measured  and  stored  on  ice.  This  material  contained  in  all  152.3  grams 
of  carbohydrate,  of  which  the  greater  part  was  dextrose.  The  feces  were 
collected  for  the  two  days  of  the  experiment  and  it  was  found  that  49.4  grams 
of  carbohydrate  were  unabsorbed,  thus  indicating  that  102.9  grams  had  dis¬ 
appeared,  or  67.5  per  cent  of  the  total  amount  injected. 

Stolting,  1904. — The  difference  in  the  absorption  of  various  sugars,  partic- 


1  Deucher:  Correspondenzbl.  f.  schweiz.  Aertze,  1903,  p.  41. 

2  Zehmisch:  Ausnutzung  von  Nahrklystieren,  Diss.,  Halle,  1903. 


PREVIOUS  RESEARCHES  ON  RECTAL  ALIMENTATION. 


7 


ularly  cane  sugar,  glucose,  and  milk  sugar,  was  studied  by  Stolting* 1  in  exper¬ 
iments  upon  himself.  In  the  morning  a  cleansing  enema  was  taken,  and  an 
hour  afterwards '250  c.  c.  of  a  sugar  solution,  warmed  to  body  temperature, 
was  passed  through  a  rubber  tube  into,  the  intestine  for  30  to  40  cm.  After  2 
hours  the  material  was  evacuated.  To  remove  the  sugar  remaining  in  the  in¬ 
testine,  he  passed  in  a  liter  of  water  and  then  let  it  flow  out  by  simply  lower¬ 
ing  the  tube.  Three  experiments  were  made  with  dextrose  in  which  25,  33.4, 
and  53  grams,  respectively,  were  given,  each  portion  in  250  c.  c.  of  water.  In 
the  first  experiment,  200  c.  c.  of  fluid  were  rejected  after  2  hours,  with  a  con¬ 
centration  of  3.8  per  cent,  in  contrast  to  the  10  per  cent  solution  introduced. 
No  sugar  was  found  in  the  liquid  from  the  final  cleansing  enema.  The  ab¬ 
sorption  was  17.4  grams,  or  70  per  cent.  In  the  second  experiment,  187  c.  c. 
were  passed  after  2  hours,  and  this  contained  5.2  grams  of  sugar,  with  a  con¬ 
centration  of  2.8  per  cent.  The  water  from  the  wash-out  contained  1.7 
grams.  The  absorption  was  27  grams,  or  about  79  per  cent.  In  the  third 
experiment  the  material  which  was  rejected  after  2  hours  contained  23.8 
grams  of  sugar,  with  a  concentration  of  7.9  per  cent,  in  contrast  to  the  concen¬ 
tration  of  the  solution  injected  of  slightly  over  20  per  cent.  The  liquid  from 
the  wash-out  contained  only  0.9  gram,  so  that  the  total  sugar  unabsorbed  was 
24.7  grams,  with  an  absorption  of  28.1  grams,  or  53  per  cent. 

Arnheim,  1905. — In  4  experiments  with  a  diabetic  patient,  Arnheim2  in¬ 
troduced  from  35  to  50  grams  of  dextrose  in  a  30  per  cent  solution.  The 
observations  were  scattered  over  a  period  of  5|  weeks.  At  the  beginning  of 
the  period,  the  patient  was  eliminating  large  quantities  of  sugar  and  had 
acidosis,  and  excreted  sugar  practically  the  entire  time  of  observation.  The 
upper  part  of  the  intestine  was  separated  from  the  lower  by  means  of  a 
dilatable  tampon,  so  that  a  section  of  about  8  to  10  cm.  at  the  lower  end  was 
available  for  the  absorption  of  the  sugar  solution.  After  the  first  experiment, 
in  which  35  grams  were  given  in  a  30  per  cent  solution,  there  was  a  slight  in¬ 
crease  in  the  sugar  elimination  (6  grams),  but  this  increase  did  not  correspond 
to  the  amount  of  the  injection.  The  acidosis  also  decreased  and  disappeared 
on  the  second  day  following.  At  the  time  of  the  second  experiment  the 
patient  was  on  a  strict  diet  and  the  urine  sugar-free.  He  was  given  50 
grams  of  dextrose,  and  after  5  hours  3  grams  were  recovered.  On  the  2 
succeeding  days  there  was  no  sugar  elimination  and  the  acidosis  disappeared 
on  the  second  day.  About  a  week  later,  when  the  patient  was  again  elimi¬ 
nating  sugar,  with  40  grams  of  carbohydrate  in  the  diet,  he  was  given  50 
grams  of  sugar  by  rectum,  and  instead  of  rising  the  sugar  elimination  fell  and 
acidosis  decreased.  Twelve  days  later  another  50  grams  of  dextrose  was 
given,  with  no  increase  in  sugar  elimination.  The  author  believed  that  the 
greater  part  of  the  sugar  was  utilized  by  the  organism,  because  only  a  small 
part  of  the  injected  sugar  was  recovered  in  the  feces  and  there  was  no  in¬ 
crease  in  the  sugar  eliminated  in  the  urine.  He  considered  this  to  be  sub¬ 
stantiated  by  the  decrease  in  the  acidosis,  but  was  uncertain  as  to  whether 
the  sugar  was  utilized,  because  in  its  absorption  it  did  not  pass  through  the 
liver  or  because  the  sugar  was  absorbed  slowly. 

Bingel,  1905. — Four  diabetics  were  used  as  subjects  by  Bingel3  in  a  study 
of  the  elimination  of  sugar  and  the  acetone-diacetic  acid  reaction  after  the 
rectal  injection  of  a  dextrose  solution.  A  diet  was  given  the  subjects  to 
bring  them  to  a  constant  sugar  elimination. 

With  case  I  the  elimination  of  sugar  was  approximately  70  grams  per  day. 

1  Stolting:  Ueber  den  Wert  verschiedener  Zuckerarten  als  Bestandteil  von  Nahrklystieren.  Diss., 
Halle,  1904. 

1  Arnheim:  Zeitschr.  f.  diat.  u.  physikal.  Therapie,  1905,  8,  p.  75. 

*  Bingel:  Die  Therapie  der  Gegenwart,  1905,  p.  436. 


8 


HUMAN  METABOLISM  WITH  ENEMATA. 


On  the  third  day  35  grams  of  dextrose  were  given  in  100  c.  c.  of  distilled 
water  and  an  attempt  was  made  to  exclude  the  upper  part  of  the  large  in¬ 
testine  by  means  of  a  tampon,  as  Arnheim  had  done.  The  patient  was 
unable  to  retain  the  enema  longer  than  lj^  hours.  The  stool  contained  31 
grams  of  sugar,  so  that  apparently  only  4  grams  were  absorbed.  The  next 
day  45  grams  were  given  in  100  c.  c.  of  water  according  to  the  same  method. 
This  amount  was  retained  for  only  45  minutes  and  rejected,  there  being  42.5 
grams  of  sugar  in  the  stool.  Bingel  thereafter  injected  the  sugar  without 
attempting  to  separate  the  upper  and  lower  parts  of  the  intestine,  30  grams 
and  50  grams  of  sugar  being  given  to  the  subject.  There  was  no  increase  in 
the  sugar  elimination,  and  no  change  in  the  diacetic  acid  reaction. 

With  case  II,  the  sugar  elimination  was  69  grams  at  the  beginning  and 
later  fell  to  36  grams;  then  50  grams  of  sugar  were  given  by  rectum,  but  the 
sugar  elimination  did  not  increase.  Similarly,  rectal  feeding  was  used  at 
intervals,  over  a  period  of  10  days  and  the  sugar  elimination  gradually  de¬ 
creased  to  4.5  grams.  The  author  says  that  the  absence  of  sugar  in  the  urine 
after  giving  it  by  rectum  was  not  due  to  better  utilization,  but  to  an  increase 
in  tolerance.  Two  other  patients  were  treated  in  a  similar  manner,  as  much 
as  60  grams  of  dextrose  per  day  being  given  rectally  without  apparent  in¬ 
fluence  upon  the  sugar  elimination. 

Believing  that  the  disappearance  of  sugar  was  partly  due  to  fermentation, 
he  made  several  experiments  in  an  attempt  to  demonstrate  this.  In  one,  30 
grams  of  sugar  in  300  c.  c.  of  a  salt  solution  were  fermented  with  feces  5 
hours  and  there  still  remained  19.5  grams  of  sugar;  in  another  experiment 
with  50  grams  of  sugar,  there  still  remained  36  grams.  He  concludes  that 
fermentation  may  play  a  role,  but  is  uncertain  whether  the  action  is  the  same 
in  the  intestine  as  in  a  fermentation  experiment.  The  nitrogen  elimination 
was  not  apparently  influenced  in  any  way  by  the  rectal  ingestion  of  sugar. 
He  concludes  that  as  the  acidosis  was  not  reduced,  there  is  no  direct  proof 
that  the  sugar  is  better  utilized  and  believes  that  the  use  of  rectal  injection  of 
dextrose  in  diabetes  is  problematical. 

Hausmann,  1905. — Hausmann1  undertook  to  prove  or  disprove  the  work 
of  Stolting.  (See  p.  6.)  No  food  was  given  the  evening  before,  and  on  the 
morning  of  the  experimental  day  a  cleansing  enema  was  taken.  About  1 
hour  later  the  experimental  enema  was  given.  Hausmann  used  a  soft  in¬ 
testinal  tube  a  few  centimeters  in  length;  the  volume  of  the  injection  was 
always  about  250  c.  c.,  and  the  enemas  were  retained  for  about  2  hours, 
except  when  peristalsis  started.  He  used  1  or  2  liters  of  water  for  washing 
out  the  sugar  remaining  in  the  intestine.  The  main  purpose  of  the  experi¬ 
ments  was  to  compare  the  absorption  and  the  subjective  impressions  of  the 
subjects  with  dextrose  with  those  which  were  obtained  with  cane  sugar  and 
milk  sugar.  Only  the  experiments  with  dextrose  are  considered  here. 

In  the  two  experiments  with  a  10  per  cent  dextrose  solution,  the  highest 
absorption  was  79  per  cent  of  the  total  amount  injected;  with  a  15  per  cent 
solution  the  highest  absorption  was  60  per  cent.  The  largest  amount  of 
dextrose  absorbed  was  24  grams.  Two  experiments  with  a  20  per  cent  con¬ 
centration  were  made.  In  one  the  enema  was  expelled  after  45  minutes; 
the  sugar  elimination  was  not  determined.  In  the  other  experiment,  the 
solution  was  retained  1  hour;  21.3  grams  or  39.9  per  cent  of  the  dextrose  was 
absorbed.  In  the  second  series,  10  per  cent  of  alcohol  was  added  to  a  10  per 
cent  dextrose  solution;  the  highest  absorption  in  three  experiments  was  76 
per  cent,  thus  indicating  no  increase  in  absorption  due  to  the  addition  of 
alcohol.  Two  experiments  were  made  with  a  15  per  cent  dextrose  solution 

1  Hausmann:  Experimen telle  Untersuchungen  iiber  die  Ausnutzung  verschieden  zusammenge- 
setzer  Zuckerclysmen.  Diss.,  Halle,  1905. 


PREVIOUS  RESEARCHES  ON  RECTAL  ALIMENTATION.  9 

to  which  1  per  cent  of  sodium  chloride  was  added;  this  made  practically  no 
difference  in  the  absorption,  either  in  amount  or  in  per  cent. 

Studies  were  likewise  made  with  solutions  of  various  temperatures.  With 
a  15  per  cent  dextrose  solution  at  39°  C.,  the  absorption  was  59  per  cent  of 
the  total,  while  with  the  same  concentration,  but  a  temperature  of  41.5°  C., 
the  absorption  was  70  per  cent  of  the  total.  The  amounts  injected  and  the 
amounts  absorbed  were  fairly  comparable  to  those  which  were  used  in  the 
study  reported  in  this  monograph. 

Heile,  1905. — In  experimental  observations  upon  absorption  in  the  small 
and  large  intestines,  Heile* 1  conducted  a  number  of  experiments  with  a 
glucose  solution  on  a  dog  which  had  been  operated  upon  to  exclude  the  small 
from  the  large  intestine,  and  also  with  a  patient  on  whom  an  operation  had 
been  performed  in  such  a  way  as  to  produce  an  anus  prceternalis .  This  made 
available  the  lower  section  of  the  large  intestine  which  could  be  used  for 
absorption  experiments.  Two  experiments  were  made  with  the  patient. 
In  one  an  injection  was  given  of  140  c.  c.  of  a  9.3  per  cent  solution,  containing 
13.6  grams  of  glucose.  It  was  retained  an  hour.  The  material  from  the 
wash-out  contained  11.77  grams  of  sugar,  with  a  consequent  absorption  of 
1.83  grams.  With  165  c.  c.  of  a  16.4  per  cent  solution,  containing  27.1  grams, 
the  absorption  was  but  5.9  grams  in  the  same  time.  There  were  three 
experiments  with  the  dog.  The  volumes  of  the  injection  were,  respectively, 
77,  70,  and  77  c.  c.,  in  concentrations  of  5.0,  5.1,  and  8.3  per  cent.  The 
absorption  was  0.87,  1.16,  and  1.36  grams.  Heile  points  out  that  the 
absorption  with  the  man  was  extremely  small,  and  he  does  not  believe  it  to 
be  of  much  significance  with  rectal  feeding.  The  values  for  the  dog  were 
relatively  much  better. 

Orlowski,  1905. — ’The  effect  of  rectal  injection  of  dextrose  solution  upon 
the  sugar  elimination  of  diabetics  was  also  studied  by  Orlowski.2  The 
patients  were  put  on  a  constant,  usually  carbohydrate-free  diet,  and  when 
the  sugar  elimination  in  the  urine  had  reached  an  approximately  constant 
value,  they  received  by  rectum  at  first  50  grams  of  dextrose  and  on  other 
days  double  this  quantity.  For  comparison  of  results,  a  similar  quantity  of 
sugar  was  given  by  mouth.  An  examination  of  the  stools  after  the  enemas 
brought  out  the  surprising  fact  that  with  one  exception  only  50  per  cent  of 
the  sugar  was  actually  absorbed. 

With  case  I,  on  a  strict  diet,  the  sugar  elimination  was  25  grams  per  day; 
at  10  o’clock  in  the  morning  of  the  next  day,  50  grams  of  glucose  were  given 
by  rectum  and  the  sugar  elimination  for  that  day  was  20  grams.  The  follow¬ 
ing  day,  with  strict  diet,  the  sugar  elimination  was  16  grams.  On  the 
succeeding  day,  50  grams  of  glucose  were  given  by  mouth  and  the  sugar  elimi¬ 
nation  rose  to  62  grams.  The  next  day,  with  strict  diet,  the  sugar  elimi¬ 
nation  was  37  grams.  On  the  last  day,  50  grams  of  glucose  were  injected  by 
rectum  and  the  sugar  elimination  was  only  33  grams.  The  other  cases 
showed  results  of  similar  character,  even  when  100  grams  were  given. 

The  author  found  that  sugar  by  rectum  was  not  effective  in  the  reduction 
of  the  ammonia  elimination  or  of  the  acidosis  as  indicated  by  the  acetone 
elimination.  He  believes  that  some  of  the  sugar  disappears  by  bacterial 
decomposition,  but  does  not  consider  that  this  explains  all  the  results.  He 
does  not  believe  that  the  use  of  sugar  rectally  with  diabetics  is  of  great  value, 
because  it  is  not  effective  in  reducing  the  acidosis  and  it  is  difficult  for  the 
diabetics  to  tolerate  it.  A  theoretical  comparison  of  the  sugar  tolerance  of 
diabetics  with  oral  and  rectal  introduction  offers  much  of  interest,  but 
Orlowski  was  unable  to  follow  the  subject  further. 


1  Heile:  Grenzgebeite  d.  Med.  u.  Chirurg.,  1905,  14,  p.  474. 

1  Orlowski:  Zeitschr.  f.  diat.  u.  physikal.  Therapie,  1905,  8,  p.  481. 


10 


HUMAN  METABOLISM  WITH  ENEMATA. 


Satta,  1905. — In  an  extensive  study  upon  acidosis  and  acetonuria,  Satta1 
made  an  experiment  in  which  dextrose  was  injected  to  observe  the  effect 
upon  the  acetone  excretion.  The  first  day  was  a  fasting  day  and  then  two 
days  followed  with  the  subject  otherwise  fasting,  in  which  150  grams  of 
dextrose  were  given  by  rectum  each  day.  On  the  fourth  day,  240  grams  of 
cane  sugar  were  given  by  mouth.  The  elimination  of  acetone  on  the  first 
day  was  0.8  gram;  on  the  two  succeeding  days,  0.5  and  0.3  gram,  respec¬ 
tively,  and  on  the  fourth  day,  0.06  gram.  The  ammonia  excretion  was  0.5, 
0.7,  0.5,  and  0.4  gram  for  the  series  of  4  days.  The  author  concludes  that 
this  experiment  indicates  no  difference  between  the  two  methods  of  taking 
the  sugar,  by  mouth  or  by  rectum,  as  to  the  depression  or  prevention  of  ace¬ 
tonuria.  One  should  note,  however,  that  in  one  case,  150  grams  of  dextrose 
were  given  and  in  the  other  240  grams  of  cane  sugar.  The  dextrose  given 
by  rectum  apparently  prevented  an  increase  in  the  acidosis.  The  ferric- 
chloride  reaction  on  the  second  day  of  the  rectal  injection  was  negative; 
consequently  the  acidosis  did  not  increase  during  the  fasting. 

Rosenfeld,  1907. — In  a  discussion  of  the  method  of  oxidation  of  sugar, 
Rosenfeld 2  reports  the  percentage  of  glycogen  in  the  liver  in  several  experi¬ 
ments  with  a  phlorizinized  dog  in  which  the  dextrose  was  introduced  in  three 
ways  —  by  mouth,  by  rectum,  and  by  vein.  The  greatest  deposit  of  glyco¬ 
gen  was  after  the  introduction  by  mouth,  the  precentage  in  the  liver  varying 
from  3.7  to  7  per  cent.  The  next  largest  average  was  when  the  dextrose  was 
introduced  by  rectum,  the  percentage  varying  from  0  to  8.3  per  cent,  while 
by  vein  in  4  out  of  7  cases  there  was  hardly  a  detectable  amount.  Rosenfeld 
concludes  that  with  introduction  by  mouth,  the  sugar  is  oxidized  by  way  of 
the  liver,  while  with  introduction  by  vein  and  by  rectum  it  travels  in  a  non- 
hepatic  path.  Accordingly,  dextrose,  when  introduced  into  the  body,  may 
be  oxidized  either  by  passing  through  the  glycogen  stage  or  without  glycogen 
formation.  In  discussing  rectal  alimentation,  many  writers  have  quoted 
these  experiments  as  an  explanation  of  the  differences  between  the  two 
methods  of  feeding  by  mouth  and  feeding  by  rectum. 

Boyd  and  Robertson,  1906. — Boyd  and  Robertson3  made  observations  on 
6  and  7  days  upon  the  absorption  of  a  mixed  enema  given  to  6  patients.  The 
mixed  enema  contained  peptonized  milk,  eggs,  salt,  dextrose,  and  water. 
The  amounts  of  dextrose  used  in  the  enema  varied  on  the  average  from  38 
to  88  grams  and  the  absorption  from  38  to  81  grams.  The  total  energy- 
content  of  the  dextrose  varied  from  151  to  332  calories. 

Rosenfeld,  1909. — In  connection  with  some  studies  on  the  treatment  of 
diabetics,  Rosenfeld4  introduced  glucose  by  rectum.  With  one  patient  who 
was  eliminating  98  grams  of  sugar  in  the  urine  per  day,  he  added  50  grams 
of  dextrose  to  the  diet  by  rectum  on  two  days.  The  sugar  elimination  on 
the  first  day  was  100  grams,  or  practically  no  increase,  and  on  the  second 
day  the  output  actually  decreased  to  84  grams.  Thus  the  sugar  elimination 
was  apparently  not  affected  by  the  rectal  injection  of  50  grams  of  sugar. 

von  Halasz,  1910. — An  interest  in  the  absorption  of  the  various  sugars  and 
their  possible  splitting  before  absorption  led  von  Hal4sz5to  make  experi¬ 
ments  on  individuals  from  15  to  39  years  of  age  who  were  either  neurasthenics 
or  epileptics,  but  who  were  otherwise  normal,  especially  as  to  the  stomach 
and  the  intestinal  canal.  The  experiments  were  always  made  in  the  fore¬ 
noon,  subsequent  to  a  lukewarm  enema  and  urination.  The  enema  of  sugar 


1  Satta:  Beitrage  z.  chem.  Physiol,  u.  Pathol.,  1905,  6,  p.  376. 

2  Rosenfeld:  Berl.  klin.  Wochenschr.,  1907,  44,  p.  1663. 

*  Boyd  and  Robertson:  Scottish  Med.  and  Surg.  Journ.,  1906,  p.  193. 

4  Rosenfeld:  Berl.  klin.  Wochenschr.,  1909,  p.  957. 

von  Hal&sz:  Deutsch.  Arch.  f.  klin.  Med.,  1910,  98,  p.  433. 


PREVIOUS  RESEARCHES  ON  RECTAL  ALIMENTATION. 


11 


solution  was  given  by  means  of  a  soft  rubber  tube,  30  cm.  long,  which  was 
inserted  15  to  20  cm.  into  the  intestine,  with  the  open  end  of  the  tube  at¬ 
tached  to  a  glass  funnel.  The  sugar  solutions  were  made  up  with  distilled 
water,  had  always  a  volume  of  500  c.  c.,  and  varied  in  concentration,  von 
Haldsz  generally  used  10,  20,  and  30  per  cent  solutions,  and  occasionally  a 
40  per  cent  solution.  He  added  7  to  8  drops  of  tincture  of  opium  to  the 
sugar  solution  to  assist  the  patients  to  overcome  the  tendency  towards  tenes¬ 
mus.  He  believes  that  this  amount  is  sufficient  to  lessen  peristalsis,  but 
too  small  to  influence  the  absorption.  Both  the  stools  and  urine  were  col¬ 
lected  for  24  hours  after  the  experiment  and  tested  for  sugar,  the  urine 
mainly  by  polarizaton. 

In  the  series  with  dextrose,  there  were  14  observations  on  6  subjects  in 
which  the  quantity  of  dextrose  introduced  varied  in  weight  from  49  to  195 
grams,  and  the  concentration  from  10  to  40  per  cent.  The  time  of  retention 
varied  from  2  hours  to  10 Yi  hours.  In  one  case  there  was  no  defecation  for 
38  hours.  The  absorption  ranged  between  10  grams  and  144  grams.  The 
urine  was  sugar-free  the  entire  time.  The  absorption  of  sugar  was  not  only 
absolutely  but  relatively  more  intense  for  the  solutions  with  the  highest 
concentrations.  Thus,  on  the  average,  8  grams  per  hour  were  absorbed 
from  a  10  per  cent  solution  as  compared  with  25  grams  per  hour  from  a  30 
to  40  per  cent  solution;  the  absorption  was  most  active  in  the  first  period 
following  the  giving  of  the  enema. 

This  investigator  also  made  experiments  with  levulose.  There  were  7 
experiments  completed  with  4  subjects  in  which  the  solution  had  concen¬ 
trations  of  10  to  20  per  cent.  An  attempt  was  also  made  to  give  levulose  in 
a  30  per  cent  solution,  but  the  subject  was  unable  to  retain  it.  The  amount 
of  sugar  introduced  varied  from  49  grams  to  98  grams.  The  amount  ab¬ 
sorbed  varied  from  30.8  grams  to  49.6  grams.  The  24-hour  urine  collected 
in  connection  with  the  experimental  days  was  sugar-free,  von  Haldsz  points 
out  that  levulose  solutions  are  not  so  well  borne  as  dextrose,  but  here  again 
the  rate  of  absorption  was  greater  with  the  more  concentrated  solution  than 
with  the  dilute.  For  example,  with  the  10  per  cent  solution  the  average 
absorption  was  9.3  grams  per  hour,  while  with  a  20  per  cent  solution,  there 
was  an  absorption  of  38.4  grams  per  hour,  von  Haldsz  also  conducted  ex¬ 
periments  with  other  simple  sugars  as  well  as  disaccharides  and,  in  sum¬ 
marizing,  notes  that  the  absorption  of  levulose  is  relatively  most  rapid, 
with  dextrose  next  in  order. 

Gompertz,  1910. — In  order  to  determine  whether  rectal  absorption  is 
effective,  Gompertz1  gave  injections  of  potassium  iodide,  sodium  chloride, 
and  solutions  of  dextrose.  When  potassium  iodide  was  dissolved  in  100  c.  c. 
of  water  and  injected,  he  detected  iodine  in  the  urine  and  saliva  in  from  8  to 
25  minutes.  The  sodium-chloride  experiments  were  made  over  a  period  of 
several  weeks.  He  found  that  the  absorption  was  almost  as  quantitatively 
complete  as  by  oral  administration,  and  there  was  a  marked  increase  of  sodi¬ 
um  chloride  in  the  urine  but  only  a  trace  in  the  feces  after  an  injection  of  10 
grams.  The  dextrose  experiments  were  made  upon  a  patient  with  pan¬ 
creatitis.  The  solutions  were  given  over  a  period  of  2  weeks;  the  analyses 
were  made  by  Underhill.  Injections  were  carried  out  at  the  rate  of  500  c.  c. 
during  5  hours,  followed  by  a  rest  of  1  hour.  The  concentrations  used  varied 
from  3  to  15  per  cent;  the  amounts  given  varied  from  60  to  300  grams,  and 
the  amounts  absorbed  from  43  grams  to  193  grams.  In  no  instance  did 
alimentary  glycosuria  occur.  Gompertz  believes  that  enemas  composed  of 
water,  sodium  chloride,  and  dextrose  are  rational. 

Jacobsohn  and  Rewald,  1911. — It  was  the  custom  in  Klemperer's  clinic  to 


1  Gompertz:  Yale  Med.  Journ.,  1910,  17,  p.  240. 


12 


HUMAN  METABOLISM  WITH  ENEMATA. 


give  rectally  12  grams  of  glucose  with  12  grams  of  alcohol  in  300  c.  c.  of  water 
three  times  daily.  Jacobsohn  and  Rewald 1  studied  the  absorption  of  alcohol 
and  glucose  in  varying  quantities  and  varying  concentrations  when  intro¬ 
duced  rectally.  They  also  made  fermentation  experiments,  using  feces  and 
solutions  containing  sugar  and  5  per  cent  alcohol,  and  found  no  fermentation. 
The  volumes  injected  varied  from  450  to  2,000  c.  c.  and  the  time  of  retention 
from  3  hours  to  18  hours.  The  alcohol  given  ranged  between  22.5  and  100 
grams  and  the  sugar  from  22.5  to  100  grams.  Of  15  experiments  in  which 
alcohol  was  given,  traces  of  alcohol  were  found  in  the  feces  in  6  experiments, 
2.5  grams  in  one  experiment  when  92.5  grams  of  alcohol  were  given,  and  5 
grams  in  another  experiment  when  100  grams  were  given.  The  amount  of 
sugar  unabsorbed  varied  from  0  to  40  grams,  and  the  amounts  absorbed  from 
13  grams  to  100  grams.  In  7  experiments  no  sugar  was  found  in  the  wash¬ 
out,  thus  indicating  complete  absorption.  According  to  the  author’s  cal¬ 
culations,  the  total  energy  absorbed  varied  from  208  to  1,310  calories. 

Luthje,  1913. — Experiments  were  made  by  Luthje2  on  10  diabetics  in  which 
injections  were  given  of  50  to  100  grams  of  a  sugar  solution  with  a  concen¬ 
tration  of  5.4  per  cent.  Some  of  the  experiments  continued  over  a  period  of 
several  weeks.  In  one  case,  the  subject  was  given  a  vegetable  day  with  83 
grams  of  dextrose.  This  was  followed  by  16  days  of  strict  diet,  with  the 
addition  of  75  grams  of  dextrose  by  mouth  for  4  days,  81  grams  of  dextrose 
by  rectum  for  4  days,  approximately  100  grams  of  bread  for  3  days,  81  grams 
of  dextrose  by  rectum  for  1  day,  and  50  grams  of  dextrose  intravenously  1 
day,  by  mouth  2  days,  and  by  rectum  on  the  final  day.  The  elimination  of 
sugar  in  the  urine  always  increased  when  the  dextrose  was  given  by  mouth 
and  decreased  when  it  was  given  by  rectum.  During  this  series  the  sugar 
elimination  varied  from  0  to  60  grams;  the  curve  given  by  Luthje  follows 
very  clearly  the  change  according  to  the  method  of  introduction. 

A  similar  case  likewise  shows  definitely  that  when  dextrose  (100  grams) 
was  given  by  rectum,  there  was  a  fall  in  the  elimination  of  sugar,  and  when  it 
was  given  by  mouth,  there  was  an  increase.  Luthje  thought  a  possible  ex¬ 
planation  might  be  the  slowness  of  the  injection,  as  he  used  the  drop  method. 
To  test  this,  slower  oral  introduction  was  obtained  by  giving  the  sugar  by 
mouth  at  intervals  during  the  day;  but  as  the  same  difference  between  the 
two  methods  in  the  utilization  of  the  sugar  was  found,  he  concluded  that  it 
could  not  be  due  to  the  slowness  of  absorption.  This  conclusion  is  impor¬ 
tant,  as  slowness  of  absorption  by  the  rectal  method  is  frequently  offered  as 
an  explanation  for  the  good  tolerance  by  diabetics  of  sugar  introduced  by 
rectum. 

In  order  to  prove  definitely  that  the  sugar  was  actually  absorbed  and  not 
fermented  in  the  intestine,  Luthje  made  determinations  of  blood-sugar  in 
observations  on  5  subjects  in  which  the  duration  of  injection  was  from  6  to  7 
hours.  The  quantity  of  sugar  absorbed  was  from  59  to  84  grams.  The 
cases  all  showed  increases  in  blood-sugar.  For  example,  with  case  M,  the 
blood-sugar  preceding  the  injection  was  0.09  per  cent,  and  following  in¬ 
jection  it  was  0.19  per  cent.  With  another  case  it  rose  from  0.13  to  0.23  per 
cent.  With  only  one  case  was  there  no  marked  change.  To  obtain  a 
control  upon  these  results,  Luthje  injected  salt  solution  by  the  drop  method 
for  a  period  of  6  hours,  and  determined  the  blood-sugar  at  intervals,  but 
found  no  change  with  any  of  the  three  subjects. 

Another  series  of  experiments  was  made  with  dogs,  in  which  he  injected 
sugar  directly  into  the  portal  vein  or  into  the  femoral  vein.  There  were  5 
experiments.  The  duration  of  the  injection  varied  from  45  minutes  to  1J^ 


»  Jacobsohn  and  Rewald:  Die  Therapie  der  Gegenwart,  1911,  p.  119. 
s  Luthje:  Die  Therapie  der  Gegenwart,  1913,  p.  193. 


PREVIOUS  RESEARCHES  ON  RECTAL  ALIMENTATION. 


13 


hours,  and  the  quantity  of  sugar  ingested  ranged  from  11.9  to  21.6  grams. 
He  determined  the  amount  of  sugar  excreted  in  the  urine  following  these  in¬ 
jections,  and  in  every  experiment  the  amount  eliminated  when  introduced 
by  the  femoral  vein  was  less  than  the  amount  eliminated  when  the  dextrose 
was  introduced  directly  into  the  portal  circulation.  Liithje  believes  that 
these  results  open  up  an  entirely  new  set  of  physiological  questions,  and  he 
recommends  very  strongly  the  use  of  sugar  enemas  given  by  the  drop 
method  for  diabetics. 

Mutch  and  Ryffel,  1913. — The  effect  of  rectal  injection  of  peptonized  milk 
and  dextrose  was  studied  by  Mutch  and  Ryffel.1  The  subjects  were  children 
who  had  been  operated  upon  for  defective  palate.  The  colon  was  washed 
out  each  morning  after  the  rectal  feeding.  In  one  case  38.4  grams  of  glucose 
were  given  and  only  0.07  gram  recovered;  in  another  case,  34.2  grams  were 
injected  and  0.34  gram  recovered,  showing  an  apparent  absorption  of  99  per 
cent  in  each  case.  Determinations  were  made  of  the  nitrogen,  ammonia, 
creatine,  and  creatinine  in  the  urine.  With  one  of  the  patients  30  grams  of 
dextrose  were  given  by  rectum  for  3  days  and  then  60  grams  were  injected 
for  4  days.  When  the  injection  was  increased  from  30  to  60  grams,  there  was 
a  decrease  from  0.26  gram  of  creatine  per  day  to  0.11  gram.  There  was, 
however,  no  change  in  the  acetone  and  diacetic  reactions.  The  nitrogen  fell 
from  5  grams  to  2.5  grams  in  the  change  from  30  to  60  grams  of  dextrose  by 
rectum. 

Mutch  and  Ryffel  come  to  the  conclusion  from  this  series  and  from  others 
that  they  conducted  that  dextrose  per  rectum  is  as  effective  in  reducing  the 
elimination  of  creatine  and  nitrogen  as  is  carbohydrate  introduced  by  mouth, 
but  that  it  is  not  so  effective  in  reducing  the  acidosis.  This  suggests  to  them 
that  dextrose,  when  absorbed  by  the  colon,  is  to  some  extent  metabolized  in 
an  unusual  manner.  They  believe  that  the  action  of  bacteria  in  the  colon 
has  something  to  do  with  the  difference  in  metabolism  of  dextrose  introduced 
rectally,  especially  as  an  increase  in  the  urinary  excretion  of  lactic  acid  was 
found  in  one  case  after  dextrose  had  been  given  by  rectum.  While  such 
bacterial  action  does  not  appear  to  be  great,  it  is  undesirable. 

von  Willehrand,  1913. — In  studies  made  by  von  Willebrand2  upon  5  cases 
of  diabetes,  from  50  to  100  grams  of  dextrose  in  a  5  per  cent  solution  were 
injected  by  the  drop  method.  Sugar  thus  introduced  was  much  better 
utilized  than  an  equivalent  amount  of  carbohydrate  in  other  forms  taken  by 
mouth,  von  Willebrand  concludes  that  the  favorable  effect  of  rectal  in¬ 
jection  is  due  in  part  to  the  long  time  (several  hours)  over  which  the  in¬ 
jections  and  absorption  took  place;  that  the  sugar  goes  directly  into  the 
general  circulation,  avoiding  the  portal  system;  and  that  it  is  also  possible 
that  this  method  favors  the  deposit  of  sugar  in  the  organism.  In  one  obser¬ 
vation  in  which  the  patient  received  a  strict  diet  with  the  addition  of  800 
grams  of  milk  and  60  grams  of  bread,  the  sugar  elimination  in  the  urine  varied 
from  slightly  over  100  grams  to  160  grams.  The  following  5  days  he  was 
given  a  strict  diet,  together  with  80  grams  of  sugar  by  rectum;  the  sugar 
elimination  gradually  fell  until  it  was  slightly  over  20  grams  at  the  end  of  the 
5  days. 

Goodall,  1914 . — In  a  discussion  regarding  the  value  of  rectal  alimentation, 
Goodall3  reports  a  few  experiments  on  the  absorption  of  dextrose  with  vary¬ 
ing  concentrations.  In  one  case  he  gave  500  c.  c.  of  a  3  per  cent  solution, 
which  was  retained  for  5  hours,  followed  by  a  rest  of  1  hour,  and  in  24  hours, 
42  to  52  grams  were  absorbed.  With  a  10  per  cent  solution,  157  to  163  grams 

1  Mutch  and  Ryffel:  British  Med.  Journ.,  1913,  1,  p.  111. 

2  von  Willebrand:  Finska  lakaresallskapets  Handlingar,  1913,  55,  part  n,  p.  412. 

‘Goodall:  Boston  Med.  and  Surg.  Journ.,  1914,  170,  p.  41. 


14 


HUMAN  METABOLISM  WITH  ENEMATA. 


were  absorbed,  and  with  a  15  per  cent  solution,  144  to  193  grams  were  ab¬ 
sorbed  in  24  hours.  He  says  that  the  amount  destroyed  by  bacteria  under 
these  conditions  varied  between  0.5  and  1  per  cent,  and  therefore  it  is  pos¬ 
sible  to  provide  for  one-third  of  the  total  energy  requirement  while  the  body 
is  at  rest.  He  also  reports  that  alcohol  is  readily  absorbed  in  concentrations 
of  5  or  10  per  cent,  although  he  gives  no  data.  He  believes  that  an  isotonic 
solution  of  dextrose  (5.4  per  cent  solutions)  is  best  and  reports  that  over  16 
per  cent  always  causes  diarrhea. 

Bergmark,  1915. — To  compare  the  effect  on  acidosis,  carbon-dioxide  elimi¬ 
nation,  and  content  of  sugar  in  the  blood  when  dextrose  was  taken  by  rectum 
with  that  when  it  was  taken  by  mouth  or  intravenously,  Bergmark1  made  a 
series  of  experiments  with  himself  as  subject.  The  study  included  a  number 
of  absorption  experiments.  Early  in  the  morning  he  took  a  cleansing  enema, 
and  an  hour  later  a  rectal  injection  containing  100  to  125  grams  of  dextrose 
in  1  liter  of  water,  allowing  it  to  flow  in  quickly.  The  enemas  were  retained 
from  1  to  5  hours.  After  a  defecation,  two  wash-outs  were  given  with  250 
c.  c.  of  water.  The  first  was  usually  mixed  with  feces,  while  the  second, 
which  was  analyzed  for  sugar,  always  gave  negative  results.  The  amounts 
of  sugar  absorbed  in  9  experiments,  with  the  retention  time  from  47  minutes 
to  6  hours,  varied  from  65  to  105  grams.  Bergmark  also  made  three  experi¬ 
ments  with  125  grams  of  dextrose  in  which  the  drop  method  of  introduction 
was  used,  the  injection  time  varying  from  65  to  145  minutes.  The  solutions 
were  retained  from  30  to  60  minutes  after  the  injection  had  been  completed. 
The  amounts  of  sugar  absorbed  varied  from  80  to  87  grams. 

In  the  series  of  respiration  experiments,  Bergmark  first  made  10  control 
experiments  with  himself  in  a  post-absorptive  condition.  In  these  experi¬ 
ments  the  carbon-dioxide  output  per  hour  was  determined  by  the  Johansson 
method  of  alternation  with  a  Sonden-Tigerstedt  respiration  chamber.  He 
then  carried  out  three  experiments  with  100  grams  and  50  grams  of  glucose 
taken  by  mouth,  in  which  the  carbon-dioxide  production  was  determined  in 
alternate  periods.  After  100  grams  of  dextrose,  the  production  of  carbon 
dioxide  increased  14.9  grams  in  6  hours  and  after  50  grams  it  increased  in  the 
same  time  7.0  grams.  Bergmark  then  made  several  experiments  with  rectal 
injection  of  dextrose  and  determined  the  carbon  dioxide  as  in  the  previous 
series.  In  two  experiments  combined  as  one  the  absorption  of  sugar  was  93 
and  97  grams.  The  total  increase  in  carbon-dioxide  production  in  8  hours 
was  about  21  grams.  In  another  experiment  with  125  grams,  of  which  104 
grams  of  dextrose  were  absorbed,  the  carbon  dioxide  increased  11.8  grams  in 
4  hours.  Three  experiments,  in  which  the  solution  was  given  by  the  drop 
method,  also  show  increases  in  the  carbon-dioxide  production.  In  two  of 
these  the  carbon-dioxide  output  was  measured  at  the  first,  second,  fourth, 
and  fifth  hours,  with  a  total  increase  found  of  10.2  and  11.4  grams,  respective¬ 
ly.  In  the  third  experiment,  in  which  measurements  were  made  for  only  3 
hours,  the  increase  was  5.7  grams.  Bergmark  concludes  from  his  results  that 
these  experiments  show  without  doubt  that  dextrose  introduced  rectally  is 
actually  absorbed. 

Bergmark  attempted  to  determine  the  increase  in  carbon  dioxide  after 
intravenous  injection  of  dextrose  solution,  but  these  experiments  were  com¬ 
plicated  both  by  chill  and  by  an  increase  in  body-temperature,  so  that  the 
values  are  hardly  comparable  with  other  values  obtained. 

A  study  was  also  made  upon  the  effect  on  the  acetone  elimination  of  the 
ingestion  of  sugar.  The  observations  with  sugar  were  preceded  by  several 
control  days  in  which  the  acidosis  was  produced  by  diet  and  work.  On 
practically  all  of  these  days,  from  6  o’clock  in  the  morning  to  8  o’clock  in  the 


i  Bergmark:  Skand.  Arch.  f.  Physiol.,  1915,  32,  p.  355. 


PREVIOUS  RESEARCHES  ON  RECTAL  ALIMENTATION. 


15 


evening,  there  was  a  gradually  increasing  elimination  of  acetone.  In  a 
subsequent  series,  dextrose  was  given  by  mouth  in  amounts  varying  from  10 
to  40  grams.  In  the  two  experiments  with  40  grams  there  was  a  very  defi¬ 
nite  lowering  of  the  acetone  excretion. 

This  series  was  followed  by  7  experiments  in  which  dextrose  was  introduced 
rectally  in  quantities  varying  from  30  to  125  grams.  In  most  of  these  the 
acetone  excretion  was  retarded,  if  not  actually  lowered,  so  that  the  author 
concludes  that  dextrose  introduced  rectally  has  a  definite  effect  upon  the 
acidosis,  but  that  this  effect  is  not  so  immediate  and  so  marked  as  with 
similar  quantities  introduced  by  mouth.  He  believes  that  the  difference 
between  the  results  obtained  with  the  two  methods  is  not  due  merely  to 
slower  absorption  with  the  rectal  feeding,  for  in  his  rectal  experiments  with 
hourly  injections  a  large  amount  of  dextrose  was  absorbed.  Furthermore, 
these  results  were  controlled  by  mouth  experiments  in  which  6  portions  of  5 
grams  each  were  given  at  half-hour  intervals,  and  there  was  likewise  a  definite 
lowering  of  the  acetone  excretion  in  less  than  2  hours  similar  to  that  when  the 
dextrose  was  given  in  one  portion.  He  also  considers  that  another  explana¬ 
tion  that  is  usually  given  for  the  difference  between  the  results  obtained  with 
rectal  feeding  and  those  with  mouth  feeding,  i.  e.,  that  it  is  due  to  the  absorp¬ 
tion  of  the  sugar  in  the  lower  part  of  the  intestine,  so  that  it  passes  directly 
into  the  general  circulation,  likewise  is  not  tenable  as  he  believes  that  the 
solution,  especially  when  quickly  injected,  passes  into  the  upper  part  of  the 
large  intestine. 

A  few  experiments  were  made  upon  the  amount  of  sugar  in  the  blood  after 
dextrose  injection.  With  40  grams  of  dextrose  given  by  mouth,  the  sugar- 
content  increased  from  0.10  to  0.16  per  cent  in  one  case  and  in  another, 
when  the  glycogen  supply  was  reduced,  it  rose  from  0.10  to  0.20  per  cent. 
The  blood-sugar,  when  observed  after  the  rectal  introduction  of  125  grams 
of  dextrose,  of  which  65  grams  were  absorbed  with  the  subject  in  a  condition 
of  glycogen  reduction,  showed  no  appreciable  rise.  After  intravenous  in¬ 
jection  of  dextrose,  the  rise  in  blood-sugar  was  more  marked  and  immediate 
than  when  the  sugar  was  given  by  mouth. 

Jahnson-Blohm,  1915. — The  effect  on  blood-sugar  of  the  ingestion  of 
dextrose  by  mouth  or  by  rectum  was  studied  by  Jahnson-Blohm.1  The 
subjects  were  3  healthy  individuals  and  2  diabetics.  The  sugar  solution  had 
an  isotonic  concentration.  With  the  healthy  individuals  the  dextrose  by 
mouth  was  given  both  in  one  portion  or  divided  into  several  portions,  and  by 
rectum  in  one  portion  or  by  the  drop  method.  With  the  diabetics  the 
dextrose  in  both  the  mouth  and  rectal  experiments  was  given  in  one  portion, 
the  amounts  of  dextrose  being  10  grams  by  mouth  and  30  grams  by  rectum. 
The  blood-sugar  was  determined  before  the  dextrose  was  taken,  and  then  at 
intervals  following  the  ingestion  for  a  period  of  4  hours  with  the  normal  in¬ 
dividuals  and  for  2  hours  with  the  diabetics. 

When  the  rectal  injection  was  given  the  normal  subjects  in  one  portion, 
the  dextrose  absorbed  was  49.7,  31.6,  and  46.6  grams.  With  both  the  normal 
subjects  and  the  diabetics,  the  sugar  by  mouth  produced  a  definite  rise  in  the 
blood-sugar,  this  increase  varying  with  the  amount  of  dextrose  received. 
When  the  sugar  was  introduced  rectally,  there  was  no  rise  in  blood-sugar 
with  any  of  the  subjects.  The  author  states  that  this  lack  of  utilization 
explains  why  dextrose  enemas  do  not  produce  an  increase  in  glycosuria. 
He  cites  Rosenfeld’s  conclusion  that  the  difference  in  utilization  with  oral  and 
rectal  introduction  is  caused  by  the  different  paths  in  absorption.  Jahnson- 
Blohm,  however,  does  not  believe  that  a  large  amount  of  dextrose  can  be 
taken  up  by  the  veins  in  the  lower  intestine,  but  thinks  a  real  difference 


1  Jahnson-Blohm:  Upsala  Lakareforenings  Forhandlingar,  1915,  20,  p.  331. 


16 


HUMAN  METABOLISM  WITH  ENEMATA. 


appears  in  the  behavior  of  dextrose  according  to  whether  it  is  introduced 
rectally  or  by  mouth,  although  his  experiments  offer  no  explanation. 

Mohr ,  1917. — Mohr1,  in  Luthje’s  clinic,  studied  the  use  of  rectal  injection 
of  dextrose  in  17  cases  of  diabetes;  of  these,  10  were  classed  as  light  cases, 
3  as  more  severe,  and  4  as  severe.  The  solution  had  a  concentration  of  5.4 
per  cent  and  was  given  at  body-temperature.  Injection  was  by  the  drop 
method  and  generally  extended  over  several  hours.  With  the  larger  quan¬ 
tities,  the  solution  was  divided  into  several  portions  and  quantities  as  high 
as  2  liters  were  given.  A  solution  with  the  same  concentration  was  given 
intravenously  in  10  to  15  minutes.  The  quantity  of  sugar  injected  rectally 
varied  from  27  to  200  grams.  In  those  observations  in  which  stools  were 
recovered  containing  sugar,  the  amounts  injected  were  from  54  to  108  grams, 
the  quantities  absorbed  from  these  varying  from  15  to  95  grams.  A  study 
of  the  extensive  series  of  protocols  shows  that  in  general  the  dextrose  in¬ 
jected  rectally  was  well  tolerated  by  the  diabetics.  With  the  light  cases, 
usually  no  sugar  was  eliminated  in  the  urine  or,  if  present,  there  was  no  in¬ 
crease  after  rectal  injection.  The  author  concludes  that  with  light  cases 
the  sugar  enemas  were  well  utilized  and  that  they  do  not  decrease  the  toler¬ 
ance,  that  with  severe  cases  some  sugar  is  eliminated  after  rectal  injection, 
but  the  quantity  does  not  correspond  to  the  amount  introduced  and  the 
acetone  excretion  is  slightly  less.  With  severe  cases  the  sugar  may  even 
disappear  from  the  urine  after  rectal  injection  and  the  acetonuria  be  consid¬ 
erably  lowered.  This  last  conclusion  is  hardly  justifiable  from  the  protocols. 

Hari  and  von  Halasz,  1918. — In  order  to  find  whether  or  not  sugar  is  ab¬ 
sorbed  in  the  large  intestine,  Hari  and  von  Haldsz2  used  determinations  of 
the  respiratory  exchange  rather  than  the  wash-out  method,  employing  dogs 
as  subjects.  To  avoid  the  criticism  that  the  solutions  might  pass  into  the 
small  intestine  by  anti-peristalsis,  the  dogs  were  curarized,  the  abdomen  was 
opened,  and  the  small  intestine  was  excluded  by  ligatures  at  two  points 
below  the  exit  into  the  large  intestine.  It  was  thus  impossible  for  any  mate¬ 
rial  introduced  into  the  colon  to  pass  into  the  small  intestine.  The  length 
of  the  section  available  for  sugar  absorption  was  usually  15  to  17  cms.  That 
the  ligatures  held  fast  was  proved  by  investigation  after  each  experiment. 
The  closure  of  the  rectum  was  not  complete,  as,  sooner  or  later,  some  fluid 
escaped  from  about  the  rubber  tube;  consequently,  the  investigators  were 
not  able  to  find  the  absorption  by  analysis. 

The  amounts  of  dextrose  injected  varied  from  14  to  30  grams,  with  con¬ 
centration  from  15  to  30  per  cent.  The  respiratory  exchange  was  deter¬ 
mined  by  means  of  the  Zuntz-Geppert  apparatus.  With  5  of  the  6  dogs 
experimented  on,  there  was  a  definite  rise  in  the  respiratory  quotient  above 
that  found  in  the  period  before  the  injection  took  place.  The  most  marked 
rise  in  the  respiratory  quotient  was  from  0.76  in  the  preliminary  period  to 
0.95  in  less  than  2  hours  after  injection.  At  the  end  of  5  hours  the  quotient 
had  not  returned  to  the  initial  level  and  there  was  also  a  strongly  positive 
reaction  for  sugar  in  the  urine.  With  another  dog,  the  respiratory  quotient 
rose  from  0.82  to  0.89  in  a  little  over  3  hours.  In  two  other  experiments, 
there  was  a  positive  reaction  for  sugar  in  the  urine.  Only  one  experiment 
was  unsuccessful,  its  failure  being  due  to  the  fact  that  the  sugar  solution 
leaked  out  around  the  tube  leading  into  the  rectum.  The  authors  state 
that  these  experiments  give  proof  that  such  quantities  of  dextrose  were  ab¬ 
sorbed  in  the  large  intestine  as  to  increase  the  respiratory  quotient,  thus 
indicating  a  combustion  of  sugar,  and  that  some  of  the  sugar  escaped  into 
the  urine. 


1  Mohr:  Die  Therapie  des  Diabetes  mellitus  mit  Zuckerklystieren.  Diss.,  Kiel,  1917. 

*  H&ri  and  von  Haldsz:  Biochem.  Zeitschr.,  1918,  88,  p.  337. 


PREVIOUS  RESEARCHES  ON  RECTAL  ALIMENTATION. 


17 


Fleming,  1919. — In  a  general  study  of  the  carbohydrate  metabolism  in 
ducks,  Fleming1  reports  one  experiment  giving  the  respiratory  quotient 
before  and  after  the  rectal  injection  of  dextrose.  The  apparatus  used  was 
the  Haldane  respiration  chamber  for  animals.  The  respiratory  quotient 
before  dextrose  was  given  was  0.80,  and  1  hour  after  the  injection  0.91. 
No  other  details  regarding  the  experiment  are  reported. 

Tallermann,  1920. — Tallermann 2  conducted  experiments  in  which  he  de¬ 
termined  the  sugar  in  the  blood  to  secure  evidence  of  the  absorption  of  glu¬ 
cose.  He  used  60  grams  of  dextrose  made  up  to  180  c.  c.  with  normal  saline 
solution  and  injected  it  in  10  minutes.  He  states  there  was  no  irritation, 
but  his  protocols  show  that  in  2  cases  the  material  could  not  be  retained. 
With  4  cases  the  blood-sugar  rose  after  the  injection  as  follows:  Case  I, 
from  0.094  to  0.112  in  1  hour  and  40  minutes;  case  II,  from  0.044  to  0.125 
in  1  hour  and  40  minutes;  case  IV  from  0.088  to  0.150  in  1  hour  and  15  min¬ 
utes;  and  case  V  from  0.112  to  0.138  in  1  hour.  Case  II  was  a  case  of  func¬ 
tional  vomiting,  and  the  author  believes  that  the  low  blood-sugar  at  the 
commencement  of  this  experiment  is  probably  accounted  for  by  this  con¬ 
dition.  In  about  4  hours  after  the  injection  the  blood-sugar  had  returned 
to  normal  or  below.  In  three  cases  there  was  no  rise,  but  Tallermann  be¬ 
lieves  that  the  evidence  of  a  rise  obtained  from  most  of  the  determinations 
amply  justifies  the  conclusion  that  there  is  actual  absorption  of  dextrose  by 
rectum.  In  considering  his  results,  it  must  be  noted  that  the  concentration 
used  by  him  was  very  high,  namely,  33.33  per  cent.  It  is  surprising  that 
there  was  no  irritation  and  that  most  of  the  patients  were  able  to  retain  the 
solution  without  difficulty. 

Hubbard  and  Wilson,  1922. — The  effect  of  a  rectal  injection  of  glucose 
solution  upon  the  acidosis  or  acetonuria  was  studied  by  Hubbard  and  Wilson.3 
One  of  the  authors  took  a  diet  for  4  days  in  which  the  distribution  of  energy 
was  10  per  cent  from  protein,  10  per  cent  from  carbohydrate,  and  80  per  cent 
from  fat.  Acetonuria  gradually  developed.  The  excretion  of  acetone  on 
the  day  before  the  diet  was  taken  was  0.01  gram,  while  on  the  third  day  of 
the  diet  it  was  0.22  gram.  The  beta-oxybutyric  acid  on  the  day  preceding 
the  diet  was  0.02  gram  and  on  the  third  day  of  the  diet  0.10  gram.  On  the 
morning  of  the  fourth  day  of  the  diet,  between  9h  30ra  a.m.  and  12  noon,  the 
subject  received  an  enema  consisting  of  300  c.  c.  of  a  5  per  cent  glucose 
solution,  that  is,  15  grams.  The  total  24-hour  urine  for  this  day  showed  a 
smaller  amount  of  both  acetone  and  beta-oxybutyric  acid,  particularly  of  the 
former.  The  authors  say  that  the  decrease  was  not  so  great  as  that  caused 
by  similar  amounts  of  glucose  when  taken  by  mouth.  In  an  earlier  study4 
with  the  same  distribution  of  calories  in  the  diet,  Hubbard  and  Wright  found 
with  one  case  after  4  days  of  the  diet  0.9  gram  of  beta-oxybutyric  acid  and 
0.5  gram  of  acetone.  With  two  cases  they  found  on  the  fourth  day  with  this 
distribution  of  diet,  materially  higher  amounts  of  acetone  and  beta-oxybuty¬ 
ric  acid  in  the  urine  than  on  the  fourth  day  when  glucose  by  rectum  was 
given.  The  authors  believe  that  glucose  is  absorbed  rapidly  enough  by 
rectum  to  decrease  the  excretion  of  acetone  due  to  a  diet  high  in  fat. 

Lasch,  1922. — To  determine  the  value  of  sugar  enemas  for  infants,  Lasch5 
made  4  experiments  with  4  children,  4  months  old.  In  2  of  these  experi¬ 
ments  he  injected  by  the  drop  method  200  c.  c.  of  a  20  per  cent  solution  con¬ 
taining  38  and  40  grams  of  dextrose,  respectively,  with  tincture  of  opium. 
Only  7.4  and  7.1  grams  were  absorbed,  that  is,  20  per  cent. 

»  Fleming:  Journ.  Physiol.,  1919,  53,  p.  236. 

2  Tallermann:  Quart.  Journ.  Med.,  1919-20,  13,  p.  356. 

*  Hubbard  and  Wilson:  Proc.  Soc.  Exp.  Med.  and  Biol.,  1922,  19,  p.  292. 

4  Hubbard  and  Wright:  Journ.  Biol.  Chem.,  1922,  50,  p.  361. 

•Lasch:  Klin.  Wochenschr.,  1922,  p.  1936. 


18 


HUMAN  METABOLISM  WITH  ENEMATA. 


Varela  and  Rubino,  1922. — Varela  and  Rubino 1  studied  the  results  of  the 
injection  of  100  to  200  c.  c.  of  dextrose  solutions  with  a  concentration  of  over 
40  per  cent  given  to  patients  in  the  post-absorptive  condition.  Two  hours 
before  the  beginning  of  the  experiment,  a  cleansing  enema  was  taken.  The 
sugar  solution  was  given  by  the  drop  method,  with  the  duration  of  the  in¬ 
jection  between  1  and  2  hours.  In  this  connection,  the  investigators  discuss 
the  theoretical  possibility  of  the  sugar  thus  injected  passing  into  the  general 
circulation  or  into  the  portal  circulation.  They  believe  that  with  the  drop 
method  there  is  less  likelihood  of  the  solution  entering  into  the  upper  part  of 
the  intestine,  and  therefore  not  so  much  is  likely  to  pass  into  the  portal  cir¬ 
culation,  but  if  all  the  injection  is  given  at  one  time,  it  will  probably  flow  by 
the  ampulla  and  therefore  come  into  contact  with  a  portion  of  the  circulation 
from  the  intestine  which  connects  with  the  portal  circulation. 

In  3  experiments  with  100  grams,  there  was  nearly  a  gram  of  sugar  in  the 
urine  (0.7  to  1.0  gram).  In  one  of  these  experiments  there  was  no  stool, 
consequently,  the  absorption  is  calculated  as  practically  complete,  that  is, 
99.2  grams.  In  the  other  experiments  they  recovered  31  grams  and  61  grams 
of  unabsorbed  sugar  from  the  feces  and  urine,  thus  showing  an  absorption 
of  69  grams  and  39  grams,  respectively.  When  150  grams  were  injected, 
52  grams  were  recovered  with  about  0.8  gram  in  the  urine.  In  the  case  of 
200  grams  there  was  no  recovery,  although  4.6  grams  of  sugar  appeared  in 
the  urine.  According  to  observations  with  a  concentrated  dextrose  solu¬ 
tion,  the  details  of  which  are  not  given,  the  greatest  part  of  the  absorption 
took  place  in  approximately  the  first  hour. 

Varela  and  Rubino  likewise  determined  the  blood-sugar  in  half-hour  pe¬ 
riods  for  3  hours.  The  greatest  increase  in  blood-sugar  was  with  an  injec¬ 
tion  of  150  grams  of  dextrose,  with  a  change  from  0.08  gram  to  0.13  gram 
1  hour  after  the  injection  began.  In  all  the  experiments  the  blood-sugar 
increased  slightly,  but  the  authors  conclude  that  this  change  indicates  no 
special  increase  in  glycemia  and  that  the  blood-sugar  does  not  exceed  the 
physiological  limit.  Two  of  the  subjects  who  showed  no  measurable  increase 
in  blood-sugar  with  rectal  feeding  were  given  100  grams  of  dextrose  by 
mouth  and  a  rise  was  found  in  the  blood-sugar  from  0.10  and  0.11  to  0.18 
and  0.20,  respectively,  without  the  slightest  glycosuria.  They  explain  their 
results  by  saying  that  when  the  dextrose  is  injected  by  rectum  the  greater 
part  of  the  sugar  passes  directly  into  the  general  circulation  without  going 
through  the  liver.  The  elimination  of  sugar  in  the  urine,  they  believe,  is 
due  to  the  fact  that  the  kidneys  behave  differently  towards  the  sugar  fed 
rectally  from  the  way  it  acts  towards  that  which  is  passing  through  the 
liver,  and  that  its  threshold  value  is  considerably  lower,  their  theory  being 
that  when  the  sugar  passes  through  the  liver,  a  change  of  unknown  nature 
takes  place  either  in  the  form  of  a  chemical  coupling  or  in  a  rearrangement 
within  the  molecule;  when  the  sugar  does  not  pass  through  the  liver,  the 
material  is  foreign  to  the  body  and  consequently  is  eliminated  by  the 
kidneys. 

Rubino  and  Varela,  1922. — Rubino  and  Varela,2  in  continuing  their  pre¬ 
vious  work  upon  the  effect  of  the  injection  of  dextrose  solution  on  the  blood- 
sugar  (see  above),  used  smaller  quantities  of  dextrose  and  more  dilute  solu¬ 
tions.  In  the  first  series  of  17  observations,  the  amounts  of  sugar  varied 
from  20  grams  in  a  3  per  cent  solution  to  50  grams  in  a  25  per  cent  solution, 
and  100  grams  in  a  20  per  cent  solution.  The  duration  of  the  injection 
varied  from  one-half  hour  to  3  hours.  The  blood-sugar  was  determined  for 
the  most  part  in  1-hour  intervals  for  6  hours.  In  14  out  of  the  17  observa- 

1  Varela  and  Rubino:  Med.  Klinik,  1922,  p.  831. 

*  Rubino  and  Varela:  Klin.  Wochenschr.,  1922,  p.  2370. 


PREVIOUS  RESEARCHES  ON  RECTAL  ALIMENTATION. 


19 


tions  the  blood-sugar  was  slightly  lowered.  In  the  other  3  it  rose  slightly, 
though  but  one  of  the  increases  was  really  significant  (from  0.08  to  0.13  per 
cent  in  1  hour).  In  spite  of  variations  in  concentration  and  quantities, 
therefore,  there  was  practically  no  change  in  the  blood-sugar.  To  find 
whether  a  lengthened  time  of  flow  affected  the  results,  they  made  another 
series  of  injections,  in  which  the  amounts  given  varied  from  40  to  100  grams 
in  a  5  per  cent  solution  and  the  time  of  flow  was  from  4  to  8  hours.  In  5 
out  of  the  7  observations  the  blood-sugar  was  lowered,  while  in  the  other 
2  there  was  a  very  slight  rise,  the  greatest  being  from  0.10  before  injection 
to  0.15  per  cent  8  hours  after  the  injection  began.  To  demonstrate  that 
actual  hypoglycemia  existed,  they  gave  salt  solution  in  three  experiments 
and  found  no  change  in  the  blood-sugar.  They  believe  that  the  hypo¬ 
glycemia  is  due  to  a  diminution  in  the  formation  of  sugar  by  the  liver,  and 
that  this  lessened  formation  is  dependent  upon  a  special  action  of  the  sugar¬ 
regulating  center,  in  that  it  is  possibly  affected  through  the  formation  of  a 
sugar  molecule  foreign  to  the  body  when  sugar  is  introduced  rectally.  This 
argument  is  in  line  with  the  report  of  their  previous  work,  in  which  they 
stated  the  belief  that  the  sugar  molecules  undergo  change  of  a  special  nature 
in  the  liver. 

A  series  of  5  experiments  was  made  in  which  from  20  to  40  grams  of  dex¬ 
trose  were  used  in  a  5  per  cent  solution,  with  the  duration  of  flow  from  1  to 
4  hours.  The  red  and  white  blood-cells  were  determined,  as  well  as  the 
blood-sugar.  In  3  cases  out  of  5  there  was  a  slight  increase  in  blood-sugar, 
a  decrease  in  white  cells,  and  an  increase  in  red  cells,  but,  except  in  one  ex¬ 
periment,  these  increases  and  decreases  did  not  coincide. 

In  addition  to  these  experiments  with  dextrose,  a  series  of  7  experiments 
was  made  with  levulose  in  which  Rubino  and  Varela  gave  from  20  to  120 
grams  in  solutions  varying  in  concentration  from  2.5  to  50  per  cent.  Deter¬ 
minations  in  periods  varying  from  6  to  7  hours  were  made  of  the  blood-sugar 
and  the  white  cells,  and  the  red  cells  were  also  determined  in  several  experi¬ 
ments.  The  duration  of  the  injection  varied  from  1  to  3  hours.  In  5  out  of 
7  of  the  experiments  the  greatest  variation  from  the  value  before  injection 
was  minus,  but  in  4  cases  out  of  the  7  there  was  actually  an  increase  in  the 
blood-sugar  at  some  time  during  the  period.  For  example,  with  case  No.  2, 
the  blood-sugar  at  the  beginning  was  0.10  per  cent  and  at  the  end  of  7  hours 
it  was  0.16  per  cent.  With  another  case  (No.  6)  the  preliminary  value  was 
0.08  per  cent  and  at  the  end  of  3 Yi  hours,  0.13  per  cent.  With  case  No.  7, 
it  changed  in  7  hours  from  0.08  per  cent  to  0.12  per  cent.  According  to  their 
protocols,  therefore,  there  are  more  instances  of  a  rise  in  blood-sugar  with 
levulose  than  with  dextrose. 

Another  series  of  4  experiments  was  made  in  which  40  grams  of  levulose 
in  a  5  per  cent  solution  were  given  in  1  hour,  and  comparison  made  of  the 
results  obtained  by  two  methods  of  feeding — by  mouth  and  by  rectum. 
With  ingestion  by  mouth,  the  figures  show  a  slight  increase  of  sugar  in  the 
blood,  while  with  injection  by  rectum  there  was  a  slight  lowering  or  no 
change.  A  comparison  experiment  with  dextrose,  in  which  20  grams  were 
given  in  a  2.5  per  cent  solution,  indicated  practically  no  increase  with  either 
method  of  feeding.  To  determine  whether  the  change  in  the  character  of 
the  sugar  which  they  believe  takes  place  with  ingestion  by  mouth  is  due  to 
its  being  mixed  with  secretions  from  the  duodenum,  they  carried  out  two 
experiments  with  40  grams  of  dextrose  in  a  10  per  cent  solution  and  a  period 
of  injection  of  V/i  hours,  and  determined  the  blood-sugar.  In  one  of  the 
experiments  the  solution  was  mixed  with  secretions  obtained  by  a  tube  from 
the  duodenum.  In  this  experiment  the  fall  in  blood-sugar  was  16  per  cent, 
whereas  in  the  experiment  with  no  addition  of  secretion,  the  fall  in  blood- 


20 


HUMAN  METABOLISM  WITH  ENEMATA. 


sugar  was  24  per  cent.  They  conclude  that  the  change  in  the  sugar  does 
not  take  place  in  the  small  intestine. 

Collazo,  1923. — In  a  contribution  upon  the  carbohydrate  metabolism  in 
avitaminosis,  Collazo  1  published  a  series  of  experiments  on  3  dogs  in  which 
sugar  was  injected  rectally.  One  dog  was  normally  nourished,  another  was 
fasting,  and  the  third  dog  had  been  fed  upon  a  diet  without  vitamines.  Each 
of  these  dogs  weighed  about  10  kg.  The  three  dogs  were  given  10  grams  of 
glucose  rectally;  the  concentration  is  not  reported.  Determinations  of  the 
blood-sugar  showed  that  it  fell  slightly  for  about  2  hours,  then  rose  in  all  3 
cases  until  at  the  end  of  4  or  5  hours  it  was  about  0.08  per  cent  higher  than 
at  its  lowest  point;  it  then  began  to  fall.  In  other  words,  there  was  a  slight 
increase  in  blood-sugar  which  took  place  in  about  4 Yi  hours;  the  normal 
level  was  just  about  reached  with  2  of  the  dogs  within  24  hours. 

In  another  series  of  observations  50  grams  of  glucose  were  given  in  150 
c.  c.  of  water  to  3  dogs  under  the  same  conditions  as  in  the  first  series.  The 
injection  required  about  30  minutes.  With  the  normal  dog  and  the  fasting 
dog  the  blood-sugar  rose  in  30  minutes,  with  the  former  from  0.10  to  0.25  per 
cent,  and  with  the  other  from  0.15  to  0.28  per  cent.  With  the  dog  fed  on 
the  diet  without  vitamines,  this  rise  did  not  take  place  for  V/i  hours.  With 
all  3  dogs  there  was  then  a  rapid  descent  to  normal  within  434  to  5  hours. 

RESEARCHES  WITH  RECTAL  INTRODUCTION  OF  LEVULOSE. 

There  were  but  three  researches  with  rectal  introduction  of  levulose. 
These  were  made  by  von  Haldsz2  and  by  Rubino  and  Varela3  in  connection 
with  studies  of  dextrose  injections,  and  the  results  have  already  been  given 
in  the  dextrose  section.  (See  pp.  10  and  19  and  Schuman-Leclerq,  p.  5.) 

RESEARCHES  WITH  RECTAL  INTRODUCTION  OF  ALCOHOL. 

Only  three  studies  with  alcohol  injection  by  rectum  should  be  considered 
in  this  connection.  In  one  of  these,  that  of  Jacobsohn  and  Rewald,4  a 
combination  of  dextrose  and  alcohol  was  used  and  the  results  have  been 
reviewed  in  the  dextrose  section.  (See  p.  11.)  The  other  two  studies  by 
Plantenga  and  by  Spiro  are  abstracted  here. 

Plantenga,  1898. — In  a  dissertation  published  in  1898,  Plantenga5  gives  a 
critical  review  of  previous  experimental  work  and  likewise  reports  experiments 
of  his  own  on  the  injection  of  protein,  fat,  alcohol,  and  carbohydrate  by  rectum. 
All  of  the  experiments  with  carbohydrate  were  with  cane  sugar;  consequently 
they  have  no  immediate  connection  with  the  research  reported  in  this  mono¬ 
graph.  Of  particular  interest  in  his  work  is  the  determination  of  alcohol 
absorption  in  the  colon  and  large  intestine  of  several  patients.  The  alcohol 
was  determined  by  the  specific-gravity  method.  In  one  case,  180  c.  c.  of 
liquid  containing  17.5  c.  c.  of  absolute  alcohol  were  injected;  3  hours  later  a 
wash-out  of  1  liter  was  given;  no  alcohol  was  found  in  the  fluid.  In  a  second 
case,  26.9  c.  c.  of  alcohol  in  160  c.  c.  of  liquid  were  injected,  with  a  1-liter 
enema  of  cold  water  given  45  minutes  afterwards.  In  the  1,100  c.  c.  of 
material  returned,  no  alcohol  was  found.  In  another  case  the  injection  was 
23.3  c.  c.  of  alcohol  in  350  c.  c.  of  fluid,  with  a  2-liter  enema  1*4  hours  later;  no 


1  Collazo:  Biochem.  Zeitschr.,  1923,  136,  p.  26. 

2  von  Haldsz:  Deutsch.  Arch.  f.  klin.  Med.,  1910,  98,  p.  433. 

s  Rubino  and  Varela:  Klin.  Wochenschr.,  1922,  p.  2370. 

4  Jacobsohn  and  Rewald:  Die  Therapie  der  Gegenwart,  1911,  p.  119. 

•  Plantenga:  Der  Werth  der  Nahrklystiere.  Diss.,  Freiburg,  1898. 


PREVIOUS  RESEARCHES  ON  RECTAL  ALIMENTATION. 


21 


alcohol  was  present  in  the  resulting  material.  To  obtain  further  evidence 
that  alcohol  was  actually  absorbed,  an  injection  of  100  grams  of  absolute 
alcohol  in  2  liters  of  water  were  given  to  two  patients,  the  solution  being 
warmed  to  37°  C.  The  patients  showed,  20  minutes  later,  symptoms  of  acute 
alcoholic  intoxication. 

Spiro,  1901. — The  effect  of  rectal  injection  of  alcohol  upon  the  secretion  of 
acid  in  the  stomach  was  studied  by  Spiro1  with  a  patient.  He  found  that 
rectal  injections  of  absolute  alcohol  in  quantities  of  10  c.  c.  to  200  c.  c.  in  a 
sodium-chloride  solution  or  in  alcoholic  beverages  containing  from  7  to  10 
c.  c.  of  absolute  alcohol  increased  the  acid  in  the  stomach.  The  highest 
values  were  about  one-half  hour  after  the  injection  began,  and  thereafter 
gradually  decreased. 

GENERAL  SUMMARY  OF  LITERATURE  ON  RECTAL 

ALIMENTATION. 

A  survey  of  the  literature  on  rectal  alimentation  shows  that  in  general 
there  are  indications  of  a  significant  disappearance  of  dextrose  from  the 
rectum  when  it  is  introduced  in  solutions  with  concentrations  up  to  at  least 
10  per  cent.  The  absorption  varies  with  the  quantity  introduced,  but  in 
general  the  higher  the  concentration  of  the  solution  or  the  higher  the  weight 
of  dextrose  actually  introduced,  the  higher  is  the  absorption.  A  number  of 
authors  have  considered  the  possibility  of  the  disappearance  being  due  to 
fermentation,  and  one  group  of  workers,  Mutch  and  Ryffel,  consider  that 
it  may  be  a  lactic-acid  fermentation.  The  general  opinion  seems  to  be, 
however,  that  while  there  is  admittedly  some  fermentation  of  the  dextrose 
in  the  rectum  when  it  is  introduced  in  the  ordinary  concentration,  the 
amount  which  may  disappear  by  this  process  is  too  small  to  account  for  the 
rapid  absorption  which  takes  place,  especially  in  the  first  2  hours,  as,  in 
general,  most  workers  have  found  that  the  absorption  is  more  rapid  in  the 
first  hours  than  in  the  succeeding  hours.  That  the  dextrose  is  actually  ab¬ 
sorbed  is  indicated  by  the  studies  of  respiratory  exchange,  which  give,  on 
the  whole,  definite  results  in  that  there  is  a  slight  increase  in  the  carbon- 
dioxide  elimination  after  the  introduction  of  dextrose  by  rectum.  The  most 
marked  increase  was  with  dogs,  but  the  experiment  was  conducted  under 
somewhat  unusual  conditions,  the  dogs  being  curarized  and  the  abdomen 
being  operated  upon. 

The  investigations  with  regard  to  blood-sugar  are  not  wholly  conclusive, 
because  in  2  instances  out  of  5  negative  results  were  found.  In  the  sixth 
instance,  the  study  by  Rubino  and  Varela,  the  amount  of  sugar  introduced 
was  so  large  that  the  results  are  not  comparable  to  those  of  the  other  exper¬ 
iments. 

The  general  conclusion  as  to  the  most  favorable  solution  to  use  is  that  a 
concentration  of  10  per  cent  or  under  is  preferable. 

The  evidence  regarding  the  effect  upon  acidosis  is  conflicting,  but  slightly 
in  favor  of  a  small  though  definite  influence. 

Glycosuria  was  rarely  found  in  these  investigations  unless  the  material 
was  introduced  in  such  a  way  that  the  path  of  absorption  was  restricted  to 
the  lower  portion  of  the  intestines. 

Of  unusual  interest  is  the  fact  that  in  most  of  the  investigations  with  dia- 


1  Spiro:  Muench.  Med.  Wochenschr.,  1901,  p.  1871. 


22 


HUMAN  METABOLISM  WITH  ENEMATA. 


betics,  the  subjects  were  found  to  tolerate  dextrose  by  rectum  better  than 
dextrose  given  by  mouth.  For  academic  interest  only,  it  would  be  worth 
while  to  investigate  this  particular  point  by  studies  which  would  be  thorough 
and  continued  sufficiently  long  to  demonstrate  the  better  tolerance  with 
rectal  injection. 

The  general  explanation  regarding  rectal  introduction  seems  to  be  that 
the  path  of  absorption  is  such  that  it  avoids  the  portal  circulation  and  the 
substance  is  taken  into  the  systemic  circulation,  consequently  the  point  of 
utilization  would  be  somewhat  different. 

With  levulose  there  were  but  few  investigations,  and  these  were  usually 
combined  with  the  studies  on  dextrose.  The  results  are,  in  general,  the 
same  as  was  found  with  dextrose,  with  no  difference  in  effect  with  the 
levulose. 

The  small  number  of  investigations  upon  the  rectal  use  of  alcohol  or  alco¬ 
hol-containing  materials  indicates  the  need  of  study  of  the  effect  of  rectal 
injection  of  this  substance,  particularly  in  view  of  the  fact  that  in  the  past, 
at  least,  it  has  been  a  very  general  practice  to  use  wine,  brandy,  and  other 
alcohol-containing  liquids  in  rectal  injection. 

PLAN  AND  METHODS  OF  STUDY  WITH  RECTAL 
FEEDING  OF  ALCOHOL  AND  SUGARS. 

In  this  study  of  the  effect  of  introducing  various  substances  into  the  rec¬ 
tum,  there  were  two  main  series  of  observations,  these  being  (1)  the  propor¬ 
tion  absorbed  of  the  material  introduced,  and  (2)  the  respiratory  exchange 
preceding,  during,  and  following  the  period  of  rectal  alimentation.  In 
addition,  supplementary  observations  were  made  on  the  effect  of  the  rectal 
injection  upon  the  volume  and  composition  of  the  urine,  and  the  percentages 
of  elimination  and  concentration  of  the  substance  in  the  urine.  For  com¬ 
parison,  studies  were  also  made  when  like  substances  were  taken  by  mouth. 


Table  1. — Statistical  data  for  subjects  used  in  rectal  feeding  studies. a 


Subject. 

Age. 

Height. 

Body- 

weight. 

Basal 
pulse-rate 
per  min. 

Basal 

carbon-dioxide 
production 
per  min. 

Basal 
oxygen 
absorption 
per  min. 

Basal  heat- 
production 
per  24  hours. 

yrs. 

cm. 

kg. 

c.  c. 

c.  c. 

cals. 

A 

23 

169 

54.0 

64 

157 

206 

1410 

B 

24 

176 

73.3 

59 

200 

247 

1712 

C 

24 

178 

69.7 

65 

232 

285 

1980 

D 

23 

181 

58.6 

•  •  • 

•  •  • 

•  •  •  • 

°  The  data  for  the  basal  metabolism  for  subjects  A,  B,  and  C,  were  determined  in  connection 
with  this  research,  but  are  not  given  in  detail  in  this  publication.  These  average  figures  have 
been  reported  in  a  previous  compilation  of  data.  (See  Harris  and  Benedict,  Carnegie  Inst. 
Wash.  Pub.  No.  279,  1919,  p.  40,  table  C.) 

The  materials  employed  for  these  rectal  observations  were  a  0.6  per  cent 
solution  of  sodium  chloride  which  was  used  as  a  control  for  the  other  studies, 
alcohol  solutions  of  three  concentrations  (5,  7.5,  and  10  per  cent),  and  two 


PLAN  AND  METHODS  OF  STUDY. 


23 


carbohydrates — dextrose  and  levulose — which  were  likewise  given  in  solu¬ 
tions  of  varying  densities.  The  amounts  of  alcohol  used  ranged  between 
10  and  60  grams,  and  the  levulose  between  25  and  50  grams;  the  dextrose 
was  30  grams,  except  for  one  experiment  with  60  grams.  The  levulose,  and 
usually  the  dextrose,  were  given  in  a  0.6  per  cent  solution  of  sodium  chloride; 
the  alcohol  was  diluted  with  distilled  water. 

The  subjects  were  medical  students,  presumably  in  good  health,  desig¬ 
nated  A,  B,  C,  and  D.  Subjects  A  and  C  served  in  all  the  series,  but  B  and 
D  were  used  for  only  a  part  of  the  observations.  The  age,  height,  weight, 
pulse-rate,  and  basal  metabolism  of  these  men  are  given  in  table  1.  The 
basal  figures  given  here  are  averages  of  a  number  of  results  obtained  from 
values  found  in  this  investigation,  and  only  those  values  which  were  secured 
when  the  subjects  were  in  a  post-absorptive  condition  were  utilized. 

Usually  the  man  came  to  the  Laboratory  late  in  the  afternoon,  about  4 
or  5  o’clock.  In  the  beginning  of  the  research  the  subjects  were  asked  to 
take  no  food  after  the  breakfast  of  that  day,  but  in  the  later  studies  they 
were  allowed  a  light  lunch.  In  some  instances  they  came  at  noon  and  had 
eaten  no  breakfast  or  nothing  since  breakfast.  In  a  few  cases  the  subjects 
came  early  in  the  morning  and  were  in  a  true  post-absorptive  state. 

DETERMINATION  OF  AMOUNT  OF  ABSORPTION. 

Many  of  the  absorption  studies  were  made  in  connection  with  the  obser¬ 
vations  of  the  respiratory  exchange,  but  in  no  way  interfered  with  them. 
On  his  arrival  at  the  Laboratory  the  man  was  given  a  cleansing  enema  to 
remove  all  fecal  matter  remaining  in  the  large  intestine  and  the  rectum. 
He  then  went  to  the  experimental  room  and  lay  down  on  a  couch  in  readiness 
for  the  experiment.  In  some  of  the  earlier  studies  the  observations  were 
made  with  the  subject  sitting  in  a  semi-reclining  chair.  The  catheter,  at¬ 
tached  to  a  container  of  the  substance  to  be  introduced,  was  then  inserted 
in  the  rectum,  and  the  man  remained  quiet  for  a  time  before  the  flow  of  the 
solution  was  begun.  The  period  required  for  the  complete  introduction  of 
the  material  varied  according  to  the  amount  administered,  but  was  usually 
less  than  one-half  hour,  excepting  when  large  quantities  were  given.  At 
the  end  of  the  experimental  period  another  cleansing  enema  was  given  to 
remove  all  of  the  substance  unabsorbed,  retained  for  a  few  minutes,  and 
then  expelled.  The  resulting  material  was  bottled,  preserved  with  a  layer 
of  toluol,  and  subsequently  determinations  were  made,  usually  in  duplicate, 
of  the  amount  of  the  solution  unabsorbed  in  the  rectum  which  had  been 
removed  by  the  cleansing  enema.  The  Nicloux  method,1  somewhat  mod¬ 
ified,  was  used  for  the  determination  of  the  alcohol.  (See  p.  38.)  Calcula¬ 
tions  could  then  be  made  of  the  amount  of  material  introduced  which  had 
apparently  been  absorbed. 

The  determination  of  the  unabsorbed  dextrose  and  levulose  in  the  cleans¬ 
ing  enema  was  made  by  the  S.  R.  Benedict2  method  of  reduction.  The 
method  itself  was  standardized  with  pure  dextrose. 


1  Nicloux:  Recherches  experimentales  sur  l’elimination  de  l’alcool  dans  l’organisme.  Determina¬ 

tion  d’un  “alcoolisme  congenital”.  Thesis,  Paris,  1900,  p.  7. 

2  S.  R.  Benedict:  Journ.  Biol.  Chem.,  1911,  9,  p.  57. 


24 


HUMAN  METABOLISM  WITH  ENEMATA. 


DETERMINATIONS  IN  STUDY  OF  URINE. 

The  nitrogen  in  the  urine  was  determined  by  the  Folin  macro-Kjeldahl 
method,1  and  the  sodium  chloride  by  the  Harvey2  modification  of  the  Vol- 
hard  method.  The  alcohol  eliminated  in  the  urine  after  its  injection  was 
determined  by  a  modification  of  the  Nicloux  method.  (See  p.  38.) 

DETERMINATION  OF  RESPIRATORY  EXCHANGE. 

The  majority  of  the  studies  of  the  respiratory  exchange  were  made  by  the 
gasometer  method,  but  in  a  few  comparison  experiments  the  clinical  respira¬ 
tion  chamber3  was  employed.  When  the  former  method  was  used,  two  100- 
liter  Tissot  gasometers4  were  connected  with  the  subject  in  such  a  way  that 
the  current  of  expired  air  could  be  deflected  into  the  room  or  into  the  gas¬ 
ometers  alternately.  It  was  possible  by  this  arrangement  to  collect  the 
expired  air  continuously  in  periods  of  short  duration.  The  valves  were  of 
the  Thiry-Tissot  model  and  made  entirely  of  metal.5 

In  the  earlier  experiments  the  ordinary  form  of  mouthpiece6  was  used  as  a 
breathing  appliance.  A  difficulty  arose  in  that  the  subjects,  coming  to  the 
Laboratory  as  they  did  at  the  end  of  a  day’s  activities,  were  more  or  less 
fatigued;  consequently,  when  in  a  quiet  and  relaxed  position,  they  easily 
became  drowsy  and  frequently  fell  asleep.  The  mouth  would  then  relax, 
with  a  possibility  of  leakage  of  air  around  the  mouthpiece,  thus  making  the 
measurements  of  the  ventilation  of  doubtful  value.  This  applied  more 
especially  to  subject  A.  Beginning  with  November  16,  1915,  therefore,  the 
mask7  was  adopted  as  a  breathing  appliance  and  its  successful  use  here  has 
led  to  its  general  application  in  laboratories  and  in  hospitals  where  respira¬ 
tion  studies  are  made. 

A  comparative  study 8  of  respiratory  exchange  more  recently  carried  out 
has  shown  that,  aside  from  the  fact  that  the  total  ventilation  with  the  mask 
is  slightly  higher,  the  results  obtained  with  it  are  comparable  in  every  way 
with  those  secured  with  the  mouthpiece  or  nosepiece.  The  application  of 
the  mask  made  possible  continuous  collection  of  expired  air  for  several  hours, 
also  observations  with  the  subject  asleep,  the  latter  being  very  difficult  when 
other  breathing  appliances  are  used.  With  the  mouthpiece,  the  man  usually 
sat  in  a  semi-reclining  (steamer)  chair,  but  with  the  mask  he  lay  on  a  couch. 

Analysis  of  Expired  Air. 

The  samples  of  expired  air  were  analyzed  by  means  of  the  portable  form 
of  the  Haldane  apparatus,9  and  occasionally  controlled  by  analyses  of  out- 

i  Folin  and  Wright:  Journ.  Biol.  Chem.,  1919,  38,  p.  461. 

2 Harvey:  Arch.  Intern.  Med.,  1910,  6,  p.  12. 

*  Benedict  and  Tompkins:  Boston  Med.  and  Surg.  Journ.,  1916,  174,  pp.  857,  898,  and  939. 

4 Tissot:  Journ.  de  physiol,  et  de  pathol.  gen.,  1904,  6,  p.  688. 

sThiry:  Recueil  des  travaux  de  la  soc.  med.  Allemande  de  Paris,  1865,  p.  57.  The  original 
valves  included  a  short  piece  of  large  glass  tubing.  As  this  often  became  loose,  metal  was 
substituted.  A  notch  on  one  of  the  rims  served  as  a  guide  to  the  proper  placing  of  the  valve. 
« P.  Regnard :  Recherches  experimentales  sur  les  variations  pathologiques  des  combustions  respi- 
ratoires.  Paris,  1879,  p.  286.  (See,  also,  Carpenter,  Carnegie  Inst.  Wash.  Pub.  No.  216, 
1915,  p.  54.) 

» Hendry,  Carpenter,  and  Emmes:  Boston  Med.  and  Surg.  Journ.,  1919,  181,  p.  288. 
s  Ibid.,  p.  295. 

“Haldane:  Methods  of  air  analysis.  London,  2d  ed.,  1918,  p.  47. 


PLAN  AND  METHODS  OF  STUDY. 


25 


door  air.  In  the  greater  part  of  the  work,  sodium  hydrosulphite 1  was  used 
as  an  absorbent  for  oxygen.  When  a  large  number  of  analyses  had  to  be 
carried  out  at  once,  this  reagent  proved  especially  practical  because  of  its 
power  of  rapid  absorption.  Furthermore,  the  solutionis  easily  and  quickly 
prepared  for  use. 

Method  of  Recording  Respiration-Rate  and  Activity. 

The  records  of  the  respiration-rate  were  obtained  by  the  usual  combination 
of  pneumograph  placed  around  the  thorax,  a  Marey  tambour,  and  a  kymo¬ 
graph.  The  pneumograph  around  the  thorax  also  served  to  record  the 
movements  of  the  trunk  and  arms,  while  a  second  combination,  with  the 
pneumograph  placed  around  the  upper  part  of  the  thighs,  recorded  the 
activity  of  the  lower  extremities. 

Method  of  Recording  Pulse-Rate. 

The  heart-rate  was  first  obtained  by  means  of  a  Bowles  stethoscope  at¬ 
tached  to  the  chest  over  the  apex  of  the  heart.  During  one  of  the  experi¬ 
ments  it  was  noted  that  there  were  minute  pulsations  of  the  pointer  connected 
with  the  pneumograph  around  the  thighs.  A  count  of  these  pulsations 
showed  that  they  corresponded  to  the  heart-rate  obtained  from  the  stetho¬ 
scope.  Subsequently,  arrangements  were  made  to  amplify  the  pulsations 
and  thus  obtain,  in  so  far  as  practicable,  in  every  experiment,  a  continuous 
graphic  record  of  the  pulse-rate.  For  this  purpose  a  very  light  rod  with 
maximum  leverage  was  attached  to  the  tambour;  the  end  of  this  pointer  was 
constructed  in  the  form  recommended  by  Bayliss.2  When  slight  movements 
of  the  legs  occurred,  the  record  was  interrupted. 

Benedict 3  employed  the  pneumograph  for  obtaining  pulse-records  in 
connection  with  its  use  for  determinations  of  the  respiration-rate  of  fasting 
men.  The  pneumograph  was  placed  over  the  apex  beat  of  the  heart  and  the 
pulsations  were  thus  superimposed  upon  the  slower  movements  of  the 
pointer  of  the  tambour  which  were  due  to  respiration.  In  the  earlier  experi¬ 
ments  of  the  series  a  graphic  record  was  obtained,  but  in  the  majority  of  the 
observations  the  counts  were  made  directly  from  the  pulsations  of  the  pointer. 
In  the  present  research  the  use  of  the  pneumograph  differed  from  the  pro¬ 
cedure  in  the  earlier  study  with  fasting  men  in  that  the  pulse-rates  were 
obtained  from  a  different  portion  of  the  body,  and  graphic  records  were 
secured  for  very  long  periods  of  time  without  being  contaminated  by  other 
movements. 

Apparatus  for  Detecting  Sleep. 

As  previously  stated,  very  frequently  the  subjects  became  drowsy  and 
fell  asleep,  even  in  a  sitting  position.  After  the  mask  was  substituted  for  the 
mouthpiece  and  the  lying  position  was  used,  it  was  decided  to  permit  the 
subject  to  sleep  whenever  he  was  so  inclined.  This  naturally  resulted  in 
experiments  in  which  the  subjects  were  wide  awake  in  some  periods,  sound 
asleep  in  others,  and  in  the  transitional  stage  between  these  two  conditions 
in  still  other  periods.  A  method  for  controlling  this  variation  in  degree  of 
wakefulness  was  adopted. 

1  Durig:  Biochem.  Zeitschr.,  1907,  4,  p.  65. 

*  Bayliss:  Journ.  Physiol.,  1912,  45;  Proc.  Physiol.  Soc.,  p.  xxxi. 

3  Benedict:  Carnegie  Inst.  Wash.  Pub.  No.  77,  1907,  p.  10. 


26 


HUMAN  METABOLISM  WITH  ENEMATA. 


For  this  purpose  a  signal  magnet  connected  in  series  with  a  battery  and 
time  clock  (one  minute  or  one-half  minute)  was  placed  near  enough  to  the 
subject  so  that  he  could  hear  it  operate  when  the  circuit  was  closed  and 
opened.  The  man  held  in  his  hand  a  pear-shaped  push  button  connected  to 
a  second  signal  magnet  system  which  was  independent  of  the  first,  but  which 
recorded  very  near  the  other  magnet.  He  was  instructed  to  press  the  button 
whenever  he  was  conscious  that  the  magnet  operated.  Records  were  thus 
obtained  of  the  operation  of  the  stimulus  magnet  system  and  of  the  amount 
of  the  subject’s  response.  Provided  the  stimulus  was  frequent  enough,  a 
regular  response  from  the  subject  could  be  interpreted  as  an  indication  that 
the  subject  was  wide  awake.  A  continuous  lack  of  response  showed  that  he 
was  inattentive,  drowsy,  or  sound  asleep.  Comparison  of  these  records  with 
the  course  of  the  heart-rate  supplied  a  definite  basis  for  judgment  as  to 
whether  the  subject  was  really  awake  or  sound  asleep.  This  method  of 
obtaining  a  record  of  the  degree  of  wakefulness  or  sleep  has  been  of  great 
value  in  the  interpretation  of  results  and  is  strongly  recommended  for  studies 
in  which  information  as  to  the  trend  of  the  metabolism  is  desired. 

Routine  of  Observations  of  Respiratory  Exchange. 

After  the  subject  came  to  the  room  in  which  the  respiration  experiment 
was  to  be  made,1  he  removed  such  of  his  clothing  as  would  interfere  with  the 
adjustment  of  the  apparatus  and  the  progress  of  the  observations,  and  sat 
down  in  the  chair  or  lay  down  upon  the  couch  as  directed.  Whenever 
necessary  for  comfort,  additional  covering  was  used.  The  catheter  was 
then  put  in  position,  the  recording  apparatus  adjusted,  and  the  mouthpiece 
attached  or  the  mask  applied.  The  preliminary  period  of  rest  varied  in  these 
experiments.  With  the  mouthpiece  it  was  frequently  from  30  minutes  to  an 
hour  in  length,  but  when  the  mask  was  used  the  observations  began  shortly 
after  it  was  applied.  Previous  to  the  injection,  there  were  two  or  three 
preliminary  periods  of  observation,  usually  about  10  minutes  in  duration. 
The  solution  was  then  administered  through  the  catheter  and  further  obser¬ 
vations  of  the  respiratory  exchange  made  during  this  time,  as  well  as  after 
the  introduction  of  the  substance  had  been  fully  completed.  In  all,  there 
were  from  2  to  30  experimental  periods  after  the  beginning  of  the  injection, 
with  the  total  period  of  observation  varying  in  length  from  32  minutes  to  8 
hours  5  minutes.  Records  of  the  respiration-rate,  muscular  activity,  and 
pulse-rate  were  simultaneously  made.  The  analyses  of  the  expired  air  gave 
data  as  to  the  carbon-dioxide  output  of  the  subject  and  the  oxygen  absorbed 
before,  during,  and  after  the  rectal  injection.  From  these  the  respiratory 
quotient  for  each  period  was  calculated.  The  results  subsequently  presented 
give  data  for  the  oxygen  consumption,  respiratory  quotient,  and  pulse-rate; 
for  the  clinical  respiration-chamber  experiments,  the  carbon-dioxide  produc¬ 
tion  is  also  given. 


1  See  routine  under  Determination  of  Amount  of  Absorption,  p.  23. 


ABSORPTION  OF  ALCOHOL. 


27 


ABSORPTION  OF  ALCOHOL  WHEN  INTRODUCED 

INTO  THE  RECTUM. 

In  connection  with  the  general  study  of  rectal  introduction  of  substances, 
observations  were  made  of  the  apparent  absorption  of  alcohol  when  solutions 
were  used  containing  5  per  cent,  7.5  per  cent,  and  10  per  cent  of  alcohol. 
The  greater  number  of  these  observations  were  with  the  5  per  cent  solution, 
these  being  21  in  number  and  with  all  four  of  the  subjects.  There  were  but  6 
observations  with  the  7.5  per  cent  solution  and  4  with  the  10  per  cent 
solution,  and  in  these  only  subjects  A,  C,  and  D  were  used. 

ABSORPTION  WITH  A  5  PER  CENT  ALCOHOL  SOLUTION. 

The  results  of  the  absorption  experiments  with  the  5  per  cent  alcohol 
solutions  are  given  in  table  2.  This  records  the  dates  of  the  experiments, 

Table  2. — Absorption  of  5  per  cent  alcohol  solutions  when  introduced  into  the  rectum  of 

human  subjects. 


Alcohol  solution. 

Wash-out. 

Duration 

of 

injection. 

Period 

injection 

retained. 

Apparent 
absorption 
of  alcohol.® 

Sub¬ 

ject. 

Date. 

Volume. 

Weight 

of 

alcohol. 

Volume 

obtained. 

Alcohol 

found. 

1915 

c.  c. 

gm. 

min. 

h.  min. 

c.  c. 

gm. 

p.  ct. 

A 

Oct.  5 

220 

11.0 

2 

3  38 

146 

None 

100.0 

A 

Oct.  27 

300 

15.0 

5 

3  3 

525 

0.12 

99.2 

B 

Oct.  17 

300 

15.0 

#  # 

4  24 

250 

None 

100.0 

A 

Oct.  12 

320 

16.0 

11 

5  14 

384 

None 

100.0 

A 

Nov.  10 

320 

16.0 

25 

3  27 

385 

None 

100.0 

C 

Oct.  29 

320 

16.0 

5 

3  56 

415 

0.11 

99.3 

A 

Dec.  2 

420 

21.0 

.  , 

3  31 

370 

0.05 

99.8 

C 

Nov.  29 

420 

21.0 

33 

2  45 

411 

0.35 

98.3 

A 

Dec.  15 

450 

22.5 

29 

5  28 

460 

None 

100.0 

A 

Dec.  10 

470 

23.5 

19 

5  5 

322 

None 

100.0 

B 

Dec.  12 

470 

23.5 

44 

3  20 

360 

0.05 

99.8 

C 

Dec.  10 

470 

23.5 

27 

4  40 

320 

0.04 

99.8 

C 

Dec.  17 

500 

25.0 

,  . 

4  52 

500 

0.25 

99.0 

C 

Dec.  20 

500 

25.0 

22 

2  3 

355 

4.81 

80.0 

A 

1916 
May  6 

6500 

25.0 

102 

5  12 

/  c670 
l  c760 

0.08  1 
None  / 

99.7 

A 

May  16 

b500 

25.0 

87 

4  5 

/  c  1,000 
l  c765 

0.46  1 
0.05  / 

97.9 

A 

Apr.  3 

510 

25.5 

68 

4  15 

/  d450 
l  d610 

None  1 
None  / 

100.0 

D 

Feb.  25 

510 

25.5 

47 

3  17 

/  340 

1  350 

0.03  1 
None  / 

99.9 

D 

Feb.  18 

520 

26.0 

33 

3  38 

f  520 

1  1,048 

None  ) 
Not  done  / 

100.0 

C 

May  13 

/  500 
\  250 

25.0 

25.0 

30 

89 

5  24 

4  54 

c930 

c610 

0.47  1 
0.08  / 

98.9 

A 

Apr.  17 

1,020 

51.0 

270 

6  14 

/  560 

l  620 

None  1 
Not  done  / 

100.0 

0  Correction  has  been  made  for  the  amount  left  in  catheter  at  end  of  injection,  estimated  to 
be  20  c.  c.  in  volume. 

6  Solution  also  contained  30  grams  of  dextrose. 
e  800  c.  c.  given.  d  600  c.  c.  given. 


28 


HUMAN  METABOLISM  WITH  ENEMATA. 


the  volumes  of  the  solution  and  the  weights  of  the  alcohol,  the  times  re¬ 
quired  for  the  complete  introduction  of  the  liquid,  and  the  full  periods  of 
retention,  i.  e.,  from  the  beginning  of  the  injection  to  the  expulsion  of  the 
material  following  the  enema  given  to  remove  the  unabsorbed  solution  from 
the  rectum.  Data  are  also  included  for  the  volume  of  liquid  obtained  from 
this  second  cleansing  enema  or  “  wash-out”,  and  the  amount  of  alcohol  which 
it  contained,  together  with  the  percentage  of  alcohol  which  had  apparently 
been  absorbed  during  the  time  of  retention  of  the  solution. 

The  experiments  were  carried  out  between  October  5,  1915  and  May  16, 
1916.  The  volume  of  the  solution  varied  from  220  c.  c.  to  1,020  c.  c.,  and 
the  weight  of  the  alcohol  in  the  solution  from  11  to  51  grams.  These 
volumes  and  weights,  however,  include  a  small  amount  of  the  solution  re¬ 
maining  in  the  catheter  and  connections  after  the  completion  of  the  in¬ 
jection.  The  residue  was  estimated  to  be  about  20  c.  c. ;  thus  the  amount  of 
alcohol  introduced  into  the  rectum  actually  varied  from  10  to  50  grams.  In 
subsequent  calculations  of  the  amounts  of  alcohol  absorbed,  correction  has 
been  made  for  the  alcohol  which  was  not  actually  introduced.  The  duration 
of  the  period  of  injection  varied  from  2  minutes  in  the  first  experiment  (with 
A  on  October  5,  1915)  to  270  minutes  in  the  experiment  with  the  same 
subject  on  April  17,  1916.  The  amount  of  the  solution  on  the  latter  date, 
however,  was  unusually  large,  being  1,020  c.  c.  Furthermore,  it  was  not 
given  continuously  but  in  portions;  consequently  the  total  period  of  in¬ 
jection  was  more  extended.  The  next  longest  period  of  injection  was  102 
minutes  in  the  observation  with  A  on  May  6,  1916.  In  addition  to  the 
alcohol,  this  solution  contained  30  grams  of  dextrose.  In  general,  the 
period  of  injection  was  under  1  hour. 

The  time  the  solution  was  retained  varied  from  2  hours  and  3  minutes 
with  C  on  December  20  to  6  hours  and  14  minutes  with  A  on  April  17.  In 
the  latter  case,  the  entire  amount  of  alcohol  was  not  in  the  body  for  the  full 
period  of  retention,  as  the  injection  continued  over  4  hours.  The  time  of 
complete  retention  was  usually  between  3  and  5  hours. 

The  volumes  recovered  from  the  enemas  at  the  end  of  the  experiment,  i.  e., 
the  “ wash-out”,  varied  from  146  c.  c.  in  the  first  experiment  to  1,048  c.  c. 
after  the  second  wash-out  in  the  experiment  with  D  on  February  18,  1916. 
The  usual  volume  was  from  300  to  600  c.  c.  The  volume  used  for  the  wash¬ 
out  enema  at  the  end  of  the  period  of  observation  was  gradually  increased. 
In  the  three  experiments  in  May  1916,  a  definite  amount  was  given  which 
was  administered  in  duplicate,  i.  e.,  two  injections  of  800  c.  c.  each.  The 
recovery  on  May  6  with  subject  A  was  670  and  760  c.  c.  each;  on  May  16, 
with  the  same  subject,  it  was  1,000  and  765  c.  c.,  respectively;  on  May  13, 
with  subject  C,  it  was  930  and  610  c.  c.,  respectively.  The  amount  of  alco¬ 
hol  obtained  from  the  wash-outs  varied  from  0  to  4.81  grams,  but  was 
usually  under  0.5  gram.  In  9  experiments  no  alcohol  was  found,  so  that  ap¬ 
parently  there  was  an  absorption  of  100  per  cent.  In  the  other  experiments 
this  absorption  varied  from  99.9  to  97.9  per  cent,  except  in  one  instance  (the 
experiment  with  C  on  December  20),  when  it  was  but  80  per  cent.  The 
time  of  retention  in  this  particular  experiment  was  but  2  hours  and  3  minutes 
from  the  beginning  of  the  rectal  injection,  which  required  22  minutes. 

In  conclusion,  it  may  be  stated  that  the  alcohol  in  solutions  containing 
5  per  cent  of  alcohol  and  varying  from  200  c.  c.  to  1,000  c.  c.  in  volume,  is 


ABSORPTION  OF  ALCOHOL. 


29 


almost  completely  absorbed  when  the  retention  is  4  hours  or  over,  and  it 
may  be  practically  complete  when  the  period  of  retention  is  3  hours. 

ABSORPTION  WITH  A  7.5  PER  CENT  ALCOHOL  SOLUTION. 

The  solution  containing  7.5  per  cent  of  alcohol  was  used  for  rectal  injection 
in  6  experiments  with  subjects  A,  C,  and  D,  in  the  period  between  March  1 
and  April  18,  1916.  The  results  are  given  in  table  3.  The  volume  of  the 
alcohol  solution  injected  varied  from  265  c.  c.  to  810  c.  c.,  the  alcohol-con¬ 
tent  ranging  from  19.9  grams  to  60.8  grams.  With  the  correction  of  20 
c.  c.  for  the  amount  left  in  the  catheter,  the  actual  amount  available  for  ab¬ 
sorption  was  about  1.5  grams  less.  The  duration  of  the  injection  varied 
from  18  minutes  with  C  on  March  1  to  286  minutes  with  the  same  subject 
on  April  18.  The  latter  experiment  was  longer  than  the  others  in  the  series, 
a  larger  amount  was  given,  and  the  injection  was  gradual.  In  general,  the 
period  of  injection  was  less  than  one-half  hour. 


Table  3. — Absorption  of  7.5  per  cent  alcohol  solutions  when  introduced  into  the  rectum  of 

human  subjects. 


Alcohol  solution. 

Wash-out. 

Sub¬ 

ject. 

Duration 

Apparent 

Date. 

Volume. 

Weight 

of 

alcohol. 

of 

injection. 

injection 

retained. 

Volume 

obtained. 

Alcohol 

found. 

absorption 
of  alcohol.0 

1916 

c.  c. 

gm. 

min. 

h. 

min. 

c.  c. 

gm. 

p.  ct. 

C 

Mar. 

1 

265 

19.9 

18 

3 

10 

1  480 

l  365 

0.02  1 
Not  det’d  / 

99.9 

D 

Mar. 

3 

265 

19.9 

26 

4 

4 

/  280 
\  590 

None  1 
Trace  / 

100.0 

A 

Apr. 

10 

350 

26.3 

31 

1 

0 

/  b498 

t  b  580 

0.50  1 

Trace  / 

98.0 

C 

Mar. 

22 

415 

31.1 

20 

3 

15 

f  6610 
l  6  500 

0.03  1 

None  / 

99.9 

A 

Apr. 

15 

500 

37.5 

27 

1 

4 

/  1,080 
l  670 

4.54  l 
None  / 

87.4 

C 

Apr. 

18 

810 

60.8 

286 

5 

43 

/  490 

l  530 

0.33  1 

0.02  / 

99.4 

°  Correction  has  been  made  for  the  amount  left  in  catheter  at  end  of  injection,  estimated  to  be 
20  c.  c.  in  volume. 

6  600  c.  c.  given. 


The  range  in  the  period  of  retention,  which  of  course  included  the  period 
of  injection,  was  from  1  hour  with  A  on  April  10  to  5  hours  and  43  minutes 
with  C  on  April  18.  In  the  latter  experiment,  as  the  period  of  injection 
was  over  4  hours,  the  volume  retained  in  the  early  part  of  the  observation 
was  considerably  less  than  the  810  c.  c.  given  in  the  whole  injection. 

The  material  obtained  from  the  wash-out  varied  from  280  c.  c.  to  1,080 
c.  c.,  the  volume  usually  approximating  500  c.  c.  or  over.  Two  wash-outs 
were  given  in  all  of  the  experiments,  with  a  volume  as  large  as  600  c.  c.  on 
April  10  and  March  22.  The  amounts  recovered  on  these  dates  were  498 
c.  c.  and  610  c.  c.  in  the  first  wash-out  and  580  c.  c.  and  500  c.  c.  in  the  second 
wash-out,  respectively. 

The  amount  of  alcohol  found  in  the  material  recovered  ranged  between 
0  on  March  3  with  subject  D  and  4.54  grams  with  subject  A  on  April  15, 
but  in  the  latter  case  the  time  of  retention  was  only  1  hour  and  4  minutes. 


30 


HUMAN  METABOLISM  WITH  ENEMATA. 


In  general,  the  amount  absorbed  was  over  99  per  cent,  or  practically  com¬ 
plete.  One  may  therefore  draw  the  conclusion  that  the  alcohol  in  a  solution 
containing  7.5  per  cent  of  alcohol  in  volumes  up  to  at  least  500  c.  c.  is  com¬ 
pletely  absorbed  when  the  period  of  retention  is  3  hours  or  more. 

ABSORPTION  WITH  A  10  PER  CENT  ALCOHOL  SOLUTION. 

The  4  experiments  with  the  10  per  cent  alcohol  solutions  were  made  with 
subjects  A,  C,  and  D,  in  March  1916.  The  results  are  given  in  table  4. 
The  volume  of  solution  injected  was,  in  practically  all  cases,  265  c.  c.,  which 
contained  26.5  grams  of  alcohol.  Allowing  0.8  gram  for  the  residues  in  the 
flask  and  connections,  the  amount  actually  available  for  absorption  was 
25.7  grams.  The  duration  of  the  injection  was,  in  all  cases,  under  one-half 
hour.  The  period  of  retention  varied  from  2  hours  30  minutes  to  4  hours  5 
minutes,  and  the  apparent  absorption  from  99.7  to  100  per  cent. 


Table  4. — Absorption  of  10  per  cent  alcohol  solutions  when  introduced  into  the  rectum  of 

human  subjects. 


Alcohol  solution. 

Wash-out. 

Sub¬ 

ject. 

Duration 

Period 

Apparent 

Date. 

Volume. 

Weight 

of 

alcohol. 

of 

injection. 

injection 

retained. 

Volume 

obtained. 

Alcohol 

found. 

absorption 
of  alcohol. 

1916 

c.  c. 

gm. 

min. 

h.  min. 

c.  c. 

gm. 

p.  ct. 

655 

0.05 

A 

Mar.  6 

265 

26.5 

23 

3  45 

a585 

None 

6  99. 8 

c210 

0.80 

A 

Mar.  24 

260 

26.0 

•  • 

2  30 

f  575 
l  °435 

None 
Not  det’d 

100.0 

220 

None 

C 

Mar.  8 

265 

26.5 

1 

3  13 

' 

°385 

Not  det’d 

100.0 

c  126 

0.61 

D 

Mar.  10 

265 

26.5 

24 

4  5 

/  530 

l  °437 

0.08  1 
None  / 

&99.7 

°  Second  wash-out.  6  Correction  of  0.8  gram  has  been  made  for  residue  in  flask,  etc. 

c  Rinsing  of  flask,  catheter,  and  connections. 


The  tentative  conclusion  drawn  from  these  4  experiments  in  which  ap¬ 
proximately  250  c.  c.  of  a  10  per  cent  alcohol  solution  were  injected  is  that 
when  the  solution  is  retained  234  hours  or  more  the  absorption  is  practically 
complete. 

ABSORPTION  OF  DEXTROSE  WHEN  INTRODUCED 

INTO  THE  RECTUM. 

In  addition  to  the  series  of  observations  on  the  absorption  of  alcohol 
solutions  when  introduced  into  the  rectum,  a  series  of  11  experiments  was 
made  in  which  dextrose  was  given  the  subject  in  the  same  way.  A  0.6  per 
cent  solution  of  sodium  chloride  was  used  as  the  carrier  in  9  of  the  experi¬ 
ments  and  a  5  per  cent  alcohol  solution  in  the  other  2.  The  observations 
were  made  with  subjects  A,  C,  and  D.  In  all  but  one  of  the  experiments  the 
volume  injected  was  500  to  520  c.  c.,  with  a  dextrose-content  of  30  grams. 


ABSORPTION  OF  DEXTROSE. 


31 


In  the  one  exception  (the  experiment  with  A  on  April  28,  1916),  the  volume 
was  1,000  c.  c.,  with  60  grams  of  dextrose.  The  results  are  given  in  table  5. 

For  the  30-gram  experiments,  the  time  of  flow  ranged  from  29  minutes  to 
102  minutes  and  the  time  of  retention  from  2  hours  17  minutes  to  6  hours 
24  minutes.  With  the  60-gram  experiment  the  flow  was  continued  254 
minutes  and  the  solution  was  retained  5  hours  25  minutes.  In  two  of  the 
30-gram  experiments  three  wash-outs  were  given,  in  one  experiment  the 
volume  used  for  each  wash-out  being  750  c.  c.  and  in  the  other  1,000  c.  c. 
In  the  other  experiments  two  wash-outs  were  given,  usually  of  800  c.  c.  each. 

The  amounts  recovered  from  the  wash-outs  in  the  30-gram  experiments 
ranged  from  510  c.  c.  to  1,075  c.  c.  in  the  first  wash-out  and  from  470  c.  c.  to 
1,000  c.  c.  in  the  second.  The  volume  recovered  in  the  second  wash-out 
was  smaller  than  that  given  in  7  out  of  the  10  observations,  although  the 
difference  was  not  significant  in  some  instances.  When  there  was  a  third 
wash-out,  the  recovery  was  practically  complete,  with  a  slight  excess  in  one 
experiment.  The  volumes  given  are  large  enough  to  obtain  significant 
results,  as  Case1  recommends  that  enemas  of  not  more  than  1,000  c.  c.  be 
given  in  most  tests.  With  the  60  grams  of  dextrose,  the  amounts  recovered 
in  the  two  wash-outs  were  1,020  c.  c.  and  797  c.  c.,  respectively. 

The  sugar  determined  in  the  first  enemata  in  the  30-gram  observations 
varied  from  1.8  grams  to  11.1  grams  and  that  determined  in  the  second 
enemata  from  0  in  4  experiments  to  3.5  grams  with  subject  D  on  May  15. 
Thus,  for  exact  results,  a  second  wash-out  is  required,  at  least  with  dextrose 
solutions  of  this  volume  and  with  these  periods  of  retention.  With  the 
third  wash-out,  the  amount  determined  was  0  in  one  30-gram  experiment 
and  0.9  gram  in  the  other.  There  is  therefore  a  possibility  with  dextrose 
that  some  sugar  will  still  remain  in  the  rectum  even  after  two  wash-outs. 
The  60-gram  experiment  showed  20  and  4.2  grams  of  sugar  for  the  first 
and  second  wash-outs,  respectively. 

The  amounts  of  dextrose  apparently  absorbed  during  the  time  of  retention 
ranged  in  the  30-gram  experiments  from  17.5  to  26.3  grams,  and  in  the  60- 
gram  experiment  it  was  34.6  grams.  In  calculating  the  amount  of  dextrose 
apparently  absorbed,  correction  was  made  for  the  volume  of  the  solution 
remaining  in  the  catheter  and  connections  at  the  end  of  the  flow.  On  the 
basis  of  a  number  of  measurements  under  different  conditions,  this  remainder 
was  estimated  to  be  20  c.  c.  With  the  assumption  that  this  portion  was 
of  the  same  concentration  as  the  rest  of  the  solution,  a  correction  was  made 
of  1.2  grams  on  the  original  30  grams,  leaving  28.8  grams  as  the  amount 
actually  administered.  In  two  instances  the  amounts  of  dextrose  left  in 
the  catheter  were  determined  as  0.6  and  0.75  gram,  respectively.  It  is  pos¬ 
sible,  therefore,  that  the  estimate  of  1.2  grams  is  0.5  or  0.6  gram  too  large. 

In  terms  of  percentage,  the  dextrose  apparently  absorbed  in  all  the  ex¬ 
periments,  regardless  of  the  amount  administered,  ranged  from  59  to  90  per 
cent,  the  latter  occurring  with  the  longest  period  of  retention  and  the  former 
with  the  largest  amount  given  (60  grams).  It  will  be  seen,  therefore,  that 
even  in  the  longest  observation,  when  the  period  of  retention  was  6  hours  24 
minutes,  the  dextrose  was  not  completely  absorbed.  In  five  of  the  eight 
30-gram  experiments  in  which  the  time  of  retention  was  over  4  hours,  the 
dextrose  apparently  absorbed  was  over  70  per  cent,  so  that  to  some  extent 


xCase:  Medical  Clinic  of  Chicago,  Jan.,  1917,  2,  p.  845. 


■Absorption  of  dextrose  when  introduced  into  the  rectum  of  human  subjects. 


32 


HUMAN  METABOLISM  WITH  ENEMATA 


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ABSORPTION  OF  DEXTROSE. 


33 


the  period  of  retention  had  a  certain  relation  to  the  amount  of  absorption. 
This  is  borne  out  by  the  fact  that  the  highest  percentage  of  absorption  was 
found  after  the  longest  period  of  retention  and  one  of  the  lowest  percentages 
was  obtained  with  the  shortest  period. 

When  the  time  element  is  taken  into  consideration  and  the  amount  ab¬ 
sorbed  per  hour  is  calculated,  it  is  found  that  this  ranged  from  4.0  to  7.8 
grams  in  the  30-gram  experiments  and  was  6.4  grams  in  the  60-gram  experi¬ 
ment.  In  most  of  the  experiments  it  was  between  4  and  5  grams  per  hour. 
The  lowest  amount  per  hour  was  found  in  one  of  the  alcohol-dextrose  ex¬ 
periments,  with  a  period  of  retention  of  5  hours  12  minutes;  the  highest 
amount  per  hour  was  for  one  of  the  sodium  chloride  and  dextrose  30-gram 
experiments  with  the  shortest  period  of  retention  (2  hours  17  minutes).  The 
experiment  with  the  longest  period  of  retention  (6  hours  24  minutes)  gave 
almost  the  lowest  amount  per  hour. 

It  is  seen  from  the  above  that,  even  with  the  longest  periods  of  retention, 
the  absorption  was  never  complete  in  these  observations  and  that  the  great¬ 
est  part  of  the  absorption  took  place  early  in  the  retention  period.  Conse¬ 
quently,  this  is  not  a  purely  mathematical  relationship  in  the  sense  that 
with  additional  hours  of  absorption  the  factor  of  division  becomes  larger  and 
the  amount  per  hour  proportionately  reduced.  If  the  absorption  period 
were  24  hours  (when  presumably  the  absorption  would  be  complete),  and 
this  figure  were  used  as  the  divisor,  mathematically  the  amount  per  hour 
would  be  much  smaller  than  any  of  the  figures  given  in  the  table.  Even  in 
the  longest  period  of  retention  the  absorption  of  the  dextrose  was  not  com¬ 
plete,  but  the  greatest  rate  per  hour  was  found  with  the  shortest  period  of 
retention,  the  total  amount  absorbed  in  the  2  hours  and  17  minutes  being 
17.8  grams.  In  the  longest  period  (6  hours  and  24  minutes),  with  the  same 
amount  of  dextrose  injected,  only  26.3  grams  were  absorbed,  an  increase  of 
but  50  per  cent  although  the  retention  period  was  almost  three  times  as  long. 
This  would  mean  that  the  amount  left  to  be  absorbed  was  much  smaller 
proportionally  than  the  amount  already  absorbed,  and  the  longer  the  period 
of  time  the  smaller  was  the  rate  per  hour,  because  the  greater  part  of  the 
absorption  took  place  in  the  first  2  hours.  Accordingly,  lengthening  the 
period  of  absorption  would  not  increase  but  decrease  the  amount  per  hour. 

Even  these  few  experiments  thus  indicate  that  the  rate  of  absorption  is 
proportional  to  the  amount  of  the  solution  present  in  the  body,  i.  e.,  the  rate 
with  30  grams  present  will  be  faster  than  with  but  10  grams  present.  Inas¬ 
much  as  these  experiments  with  a  slow  rate  of  injection  indicate  very  clearly 
that  the  absorption  was  not  uniform  from  hour  to  hour,  but  that  the  greatest 
absorption  took  place  at  the  beginning,  experiments  are  needed  to  demon¬ 
strate  whether,  if  all  the  solution  is  injected  at  once,  the  absorption  will  fol¬ 
low  a  definite  curve,  such  as  a  “  mass-law  ”  curve,  or  whether  it  will  be  uni¬ 
form  from  hour  to  hour.  These  experiments  indicate  that  there  may  be  an 
“optimum”  period  of  retention.  The  question  of  length  of  period  of  reten¬ 
tion  before  a  second  injection  should  be  given  is  of  importance  when  it  is 
desirable  to  introduce  as  much  nutrient  material  as  possible.  Experiments 
should  be  made  with  this  problem  as  a  starting-point. 


34 


HUMAN  METABOLISM  WITH  ENEMATA. 


ABSORPTION  OF  LEVULOSE  WHEN  INTRODUCED 

INTO  THE  RECTUM. 

Levulose,  although  more  rarely  used  in  rectal  alimentation,  was  included 
in  this  research  in  a  series  of  10  experiments  made  with  subjects  A,  C,  and  D. 
Like  the  dextrose,  the  levulose  was  given  in  a  0.6  per  cent  solution  of  sodium 
chloride.  In  this  series  there  were  4  experiments  with  25  grams  given  in  500 
c.  c.,  one  experiment  with  37.5  grams  in  750  c.  c.,  two  with  50  grams  in  1,000 
c.  c.,  and  three  with  50  grams  in  500  c.  c.  The  routine  of  the  experiments 
was  like  that  of  the  dextrose  observations.  The  results  are  given  in  table  6. 

The  time  of  flow  of  the  solution  varied  from  19  minutes  with  subject  C  on 
February  7  to  129  minutes  with  subject  D  on  January  28.  In  the  latter 
case  the  solution  was  1,000  c.  c.  in  volume.  When  a  volume  of  only  500  c.  c. 
was  used,  the  maximum  time  of  flow  was  100  minutes;  the  minimum  time 
with  1,000  c.  c.  was  99  minutes. 

The  time  of  retention  for  the  25  grams  varied  from  3  hours  17  minutes  to 
3  hours  32  minutes.  In  the  one  experiment  with  37.5  grams,  the  time  of 
retention  was  2  hours  48  minutes.  In  the  two  experiments  with  a  volume  of 
1,000  c.  c.  containing  50  grams  of  levulose,  the  period  of  retention  was  2 
hours  30  minutes  and  3  hours  27  minutes  respectively,  while  in  the  3  experi¬ 
ments  in  which  50  grams  were  given  in  a  volume  of  500  c.  c.  it  varied  from  1 
hour  29  minutes  to  4  hours  35  minutes.  In  the  experiment  with  the  shortest 
period  of  retention  (1  hour  29  minutes)  the  subject  was  obliged  to  urinate 
and  consequently  was  unable  to  retain  the  enema. 

In  practically  all  of  the  experiments  two  wash-outs  were  given,  or  there 
was  a  defecation  which  interrupted  the  observations.  The  volumes  of  the 
wash-outs  were  not  recorded,  as  the  value  of  such  data  was  not  at  that  time 
recognized.  When  the  amounts  that  were  recovered  with  the  defecations 
are  excluded,  those  obtained  from  the  first  wash-out  varied  from  375  c.  c.  to 
872  c.  c.;  those  from  the  second  wash-out  ranged  between  930  c.  c.  and  1,655 
c.  c.  The  amount  of  sugar  found  in  the  first  wash-out  varied  from  0  to  6.5 
grams  and  in  the  second  wash-out  from  0  in  2  cases  to  3  grams  in  1  case.  The 
amount  of  sugar  in  the  defecation  varied  from  12.0  grams  with  C  on  January 
25  to  20.4  grams  with  D  on  January  28. 

In  the  experiments  when  25  grams  were  given  and  in  which  the  times  of 
retention  were  practically  the  same,  the  amount  absorbed  was  from  16.2 
grams  to  21.8  grams,  or  68  to  91  per  cent.  In  the  one  case  with  37.5  grams, 
there  was  an  apparent  absorption  of  35.8  grams,  or  98  per  cent.  In  the  two 
cases  with  50  grams  in  1,000  c.  c.,  the  absorption  was  33.0  and  25.9  grams, 
or  67  and  53  per  cent,  respectively.  In  one  of  the  three  experiments  in 
which  50  grams  were  given  in  500  c.  c.,  there  was  apparently  complete  ab¬ 
sorption.  The  time  of  retention  in  this  observation  was  longer  than  in  any 
other  experiment  in  the  series,  i.  e.,  4  hours  35  minutes.  In  the  other  two 
experiments,  the  absorption  was  24.8  and  28.9  grams,  or  53  and  59  per  cent. 
Apparently  the  absorption  of  levulose  is  slightly  greater  than  that  of  dex¬ 
trose  with  like  conditions  as  to  the  time  of  retention  and  the  concentration. 
There  are  practically  no  experiments  with  dextrose  comparable  with  those 
with  the  50  grams  of  levulose,  but  this  greater  absorption  of  levulose  seems 
probable  from  the  apparently  complete  absorption  obtained  in  4  hours  35 


■Absorption  of  levulose  when  introduced  into  the  rectum  of  human  subjects. 


ABSORPTION  OF  LEVULOSE 


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36 


HUMAN  METABOLISM  WITH  ENEMATA. 


minutes  and  the  large  proportion  absorbed  in  the  short  periods  of  retention, 
such  as  1  hour  29  minutes,  2  hours  30  minutes,  and  2  hours  48  minutes. 

There  were  4  defecations,  that  is,  in  4  observations  after  the  injection  had 
been  completed,  the  subject  was  unable  to  retain  the  solution  in  the  colon 
and  rectum  until  the  time  for  the  first  wash-out  to  be  given.  Whether  or 
not  the  solution  was  completely  expelled  in  this  defecation  there  is  no  means 
of  knowing,  but  the  fact  that  some  sugar  was  obtained  in  the  succeeding 
wash-outs  would  indicate  incomplete  expulsion. 

The  volumes  of  the  material  expelled  varied  from  190  c.  c.  with  subject  C 
on  January  12  after  a  retention  of  1  hour  29  minutes  to  628  c.  c.  with  subject 
D  on  January  28,  after  a  retention  of  2  hours  30  minutes.  It  should  be  noted 
that  this  latter  period  of  retention  was  but  little  longer  than  the  time  of  flow. 

When  the  concentrations  of  sugar  in  these  4  defecations  are  examined,  it 
is  found  that  they  do  not  vary  widely  (see  table  7),  being  3  per  cent  for  both 
C  and  D  in  the  experiments  on  January  25  and  28,  4  per  cent  with  subject  A 
on  January  15,  and  8  per  cent  with  subject  C  on  January  12.  In  the  last 
case  the  time  of  retention  was  very  short,  only  1  hour  29  minutes.  These 
figures  indicate  that  the  levulose  was  actually  absorbed  more  rapidly  than 
the  water  in  the  solution,  or  else  that  there  was  an  actual  dilution  of  the  vol¬ 
ume  in  the  colon  and  rectum,  so  that  the  concentration  was  lowered. 


Table  7. — Concentration  of  unabsorbed  levulose  in  defecations. 


Date. 

Sub¬ 

ject. 

Levulose 

in 

solution. 

Duration 

of 

injection. 

Period 

injection 

retained. 

Volume 

solution 

introduced. 

Volume 

of 

defecation. 

Levul 

defec 

Amt. 

ose  in 
ation. 

P.  ct. 

1916 

p.  ct. 

min. 

h.  min. 

c.  c. 

c.  c. 

grams. 

Jan.  25. . 

C 

5 

99 

3  27 

1,000 

385 

12.0 

3 

Jan.  28. . 

D 

5 

129 

2  30 

1,000 

628 

20.4 

3 

Jan.  15. . 

A 

10 

29 

3  2 

500 

423 

15.9 

4 

Jan.  12.. 

C 

10 

54 

1  29 

500 

190 

15.8 

8 

In  two  of  these  experiments  with  defecations,  5  per  cent  solutions  were 
introduced  and  in  the  other  two  10  per  cent  solutions  were  used.  The  5  per 
cent  solutions,  when  calculated  on  a  basis  of  the  molecular  weight  of  levulose, 
would  give  a  depression  of  the  freezing-point  equal  to  0.522°  C.,  while  the  10 
per  cent  solution  would  give  a  depression  of  1.044°  C.  The  normal  depres¬ 
sion  of  the  blood  is  0.526°  C.,  consequently,  in  one  case,  the  solution  was 
practically  isotonic,  while  in  the  other  case  it  was  hypertonic.  Yet  in  both 
cases  the  dilution  was  such  that  the  concentration  of  the  unabsorbed  mate¬ 
rial  was  less  than  when  it  was  put  into  the  rectum.  This  might  favor  the 
second  hypothesis  that  there  was  a  dilution  of  the  solution  by  the  addition 
of  water  from  the  blood  to  the  contents  of  the  large  intestine.  On  the  other 
hand,  such  addition  appears  hardly  probable,  because  with  the  shortest 
period  of  retention  (1  hour  29  minutes)  only  190  c.  c.  were  obtained,  whereas 
500  c.  c.  had  been  injected.  Furthermore,  with  the  largest  volume  expelled, 
the  time  of  retention  (2  hours  30  minutes)  corresponded  very  closely  with 
the  time  of  flow,  while  the  difference  between  the  amount  injected  into  the 
rectum  (1,000  c.  c.)  and  the  amount  recovered  (628  c.  c.)  was  considerable. 
It  would  therefore  seem  that  the  lower  concentration  of  levulose  in  the  in¬ 
testinal  material  was  not  due  to  dilution  by  water  from  the  blood,  but  to  the 


STUDIES  OF  URINE  ELIMINATED. 


37 


fact  that  when  the  levulose  solution  was  absorbed  into  the  blood,  the  levulose 
passed  in  more  rapidly  than  the  water.  This  is  somewhat  contrary  to  the 
general  belief  that  solutions  usually  have  to  be  diluted  before  absorption 
can  take  place.  In  this  connection  it  may  be  noted  that  with  both  dextrose 
and  levulose  the  qualitative  tests  of  the  material  obtained  in  the  wash-out 
indicate  that  the  absorption  of  the  sodium  chloride  in  the  solution  was  com¬ 
plete,  even  when  some  of  the  sugar  was  found  in  the  wash-out. 

Experiments  along  this  line  are  desirable  for  comparing  the  rates  of 
absorption  of  the  levulose  when  administered  in  solutions  of  sodium  chloride 
and  in  water. 

Sufficiently  large  amounts  of  dextrose  were  given  for  the  tonicity  of  the 
solution  to  depress  the  freezing-point  0.623°  C.,  i.  e.,  the  solution  was  hyper¬ 
tonic.  Another  reason  why  levulose  is  more  rapidly  absorbed  than  dextrose 
is  the  fact  that  the  latter  is  normally  present  in  small  quantities  in  the  blood, 
whereas  levulose  is  not.  Consequently,  the  blood  would  theoretically  have 
a  greater  power  for  the  absorption  of  levulose.  However,  the  amount  of 
dextrose  in  the  blood  is  so  small  (but  0.12  per  cent)  that  it  may  be  questioned 
whether  its  presence  can  account  for  the  difference  in  the  absorption-rates 
of  dextrose  and  levulose.  Unfortunately  the  concentrations  of  the  solutions 
were  not  identical  and  so  the  experiments  are  not  strictly  comparable. 
With  levulose  the  greater  the  concentration  or  the  quantity  is,  the  greater  is 
the  absorption,  this  fact  being  apparently  independent  of  the  osmotic  pres¬ 
sure  of  the  blood. 

STUDIES  OF  URINE  ELIMINATED. 

In  addition  to  the  observations  upon  the  absorption  of  alcohol  and  the 
respiratory  exchange,  supplementary  studies  were  made  of  the  urine  elimi¬ 
nated.  These  studies  included  determinations  of  the  alcohol-content,  and 
the  volume  and  concentration  of  the  urine.  While  primarily  the  urines  were 
not  collected  for  this  particular  purpose,  but  simply  as  part  of  the  routine  of 
the  respiration  experiments  which  are  reported  and  discussed  in  the  latter 
part  of  this  monograph,  they  yet  supply  data  which  throw  additional  light 
upon  the  action  of  the  alcohol  in  the  organism  after  its  introduction  by  rec¬ 
tum. 

ELIMINATION  AND  CONCENTRATION  OF  ALCOHOL  IN  URINE 
AFTER  RECTAL  INJECTION  (LONG  COLLECTION  PERIODS). 

Alcohol  is  easily  diffusible  in  tissues  containing  water  and  in  the  living 
organism.  When  introduced  into  the  system,  it  appears  in  the  body-fluids, 
particularly  in  the  blood-stream,  and  consequently  is  to  some  extent  elimi¬ 
nated  by  action  of  the  kidneys.  Since  the  character  of  the  urinary  secretion 
is  dependent  upon  the  composition  of  the  blood,  the  presence  of  a  substance 
in  the  urine  indicates  that  it  previously  existed  in  the  blood  unless  it  was 
introduced  directly  into  the  bladder.  Proof  that  a  substance  introduced 
rectally  is  actually  absorbed  would  thus  be  supplied  by  its  identification  and 
quantitative  determination  in  the  body-fluids.  We  feel  certain,  therefore, 
that  the  appearance  of  alcohol  in  the  urine  is  absolute  proof  that  its  presence 
there  is  due  to  its  introduction  into  the  organism.  This  is  of  importance 
because  of  its  bearing  on  the  absorption  of  alcohol  by  rectum. 


38 


HUMAN  METABOLISM  WITH  ENEMATA. 


Routine  of  collection. — Early  in  the  research  determinations  were  begun  of 
the  alcohol  in  the  urine  of  the  subjects.  As  will  be  described  below,  the 
Nicloux  method,1  somewhat  modified,  was  used.  Since  the  quantities  found 
were  significant,  all  of  the  urines  were  analyzed  for  alcohol  and  the  amounts 
obtained  were  recorded.  The  usual  procedure  was  for  the  subjects  to  uri¬ 
nate  on  their  arrival  at  the  Laboratory  and  again  after  the  absorption  experi¬ 
ment  and  the  respiration  experiment  had  been  carried  out.  A  statement 
was  also  obtained  of  the  time  of  the  last  urination  before  the  subject  came  to 
the  Laboratory,  but  in  some  cases  this  record  is  deficient.  The  first  urine 
collection  was  considered  a  so-called  preliminary  or  normal  sample.  The 
second  collection  represented  a  combination  of  the  urine  secreted  by  the 
kidneys  before  the  alcohol  was  given  and  also  after  its  administration. 
Usually  the  period  of  observation  before  the  injection  was  V/2  to  2  hours, 
so  that  it  formed  a  considerable  portion  of  the  total  collection  period. 
While  it  is  recognized  that  the  urine  thus  obtained  is  not  an  unmixed  urine 
and  does  not  represent  the  actual  concentration  of  the  alcohol  in  the  urine 
after  the  injection  began,  yet  it  was  thought  that  such  records  would  be  of 
value,  particularly  in  indicating  the  amount  of  alcohol  thus  eliminated. 

Method  of  analysis. — The  urines  were  usually  distilled  under  atmospheric 
pressure  with  the  addition  of  water  and  the  distillates  collected  in  small 
portions.  The  volumes  of  urine  distilled  varied  between  10  and  50  c.  c., 
according  to  the  alcohol-content  expected.  The  volumes  of  distillate  col¬ 
lected  varied  from  10  to  25  c.  c.  and  the  5  c.  c.  usual  with  the  Nicloux  method 
was  employed  for  the  determinations  of  the  alcohol  by  direct  titration  with 
potassium-bichromate  solution.  The  procedure  was  slightly  modified  from 
that  of  the  original  Nicloux  method  in  the  following  manner:  Instead  of  mix¬ 
ing  in  the  additional  bichromate  as  it  dropped  from  the  burette,  it  was 
dropped  in,  so  that  it  rested  as  a  layer  upon  the  top  of  the  alcohol- water-sul¬ 
phuric  acid  solution.  In  this  way  the  color  of  the  added  bichromate  could 
be  compared  with  the  color  of  the  mixture  underneath  it,  and  when  such  an 
amount  had  been  added  that  there  was  apparently  no  difference  in  color 
between  the  lower  layer  and  the  supernatant  liquid,  it  was  considered  that  the 
titration  was  ended.  The  method  was  standardized  by  means  of  solutions 
of  very  dilute  alcohol  with  a  known  concentration  which  had  been  deter¬ 
mined  by  the  density  method.  It  is  considered  that  the  determinations 
are  within  =±=  5  per  cent  of  the  actual  amount  present  in  the  urine. 

Urine  with  Rectal  Injections  of  a  5  per  cent  Alcohol  Solution. 

By  far  the  greater  proportion  of  the  experiments  with  alcohol  were  with 
5  per  cent  solutions.  These  are  gathered  together  in  table  8,  which 
shows  the  statistical  data  of  the  experiments  and  their  results.  The  dates 
and  subjects,  of  course,  correspond  with  those  of  the  previously  discussed 
absorption  experiments.  The  alcohol  injected  varied  in  volume  from  220 
c.  c.  to  1,020  c.  c.  The  amount  of  alcohol  in  this  volume  varied  from  11 
grams  to  51  grams.  The  beginning  and  end  of  the  injection  are  also  stated, 
except  when  the  end-time  was  not  recorded.  The  urinary  data  comprise 
the  period  of  collection,  the  volume  of  urine  eliminated  during  this  period, 


1  Nicloux:  Recherches  experimentales  sur  [’elimination  de  l’alcool  dans  l’organisme.  Determina¬ 
tion  d’un  “alcoolisme  congenital”.  Thesis,  Paris,  1900,  p.  7. 


Table  8. — Elimination  and  concentration  of  alcohol  in  urine  over  long  periods  with  5  per  cent  alcohol  solutions  introduced  per  rectum. 


STUDIES  OF  URINE  ELIMINATED.  .  39 


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Solution  also  contained  30  grams  of  dextrose. 


40 


HUMAN  METABOLISM  WITH  ENEMATA. 


the  total  grams  of  alcohol  found  in  the  urine,  and  the  milligrams  per  cubic 
centimeter  of  urine,  i.  e.,  the  concentration.  The  percentages  of  alcohol 
thus  eliminated  in  the  urine  are  given  in  the  last  column. 

The  volumes  of  urine  eliminated  varied  from  147  c.  c.  for  C  on  November  8 
to  1,115  c.  c.  for  the  same  subject  on  May  13.  The  amount  of  alcohol 
eliminated  ranged  from  0  or  a  trace  in  the  experiments  with  A  on  May  6  and 
C  on  May  13  to  0.34  gram  in  the  second  period  of  collection  with  A  on  April 
17.  In  nearly  all  of  the  urines,  therefore,  there  was  an  appreciable  amount 
of  alcohol.  It  is  rather  surprising  that  but  a  trace  of  alcohol  was  found 
with  C  on  May  13  when  so  large  an  amount  was  injected,  also  that  none  was 
found  with  A  on  May  6.  In  the  latter  experiment  the  alcohol  was  combined 
with  30  grams  of  dextrose  in  the  same  solution.  Whether  or  no  this  had  an 
influence  upon  the  result  can  not  be  determined  from  a  single  negative  ex¬ 
periment,  particularly  when  it  was  found  in  one  case  with  C,  after  a  large 
amount  of  alcohol  had  been  injected,  that  there  was  but  a  trace  in  the  urine. 

The  results  of  the  experiment  with  alcohol  and  dextrose  suggest  the  desir¬ 
ability  of  further  investigation  on  the  effect  of  using  a  combination  of  sugar 
and  alcohol. 

The  concentration  of  alcohol  in  the  urine  varied  from  0  mg.  per  cubic 
centimeter  with  A  on  May  6  to  0.40  mg.  with  A  in  the  second  period  of 
urine  collection  on  April  17.  In  the  experiments  in  which  alcohol  was 
actually  found  in  the  urine,  the  percentage  eliminated  varied  from  0.1  per 
cent  with  A  on  October  27  and  C  on  November  8  and  29,  to  0.9  per  cent  in 
the  two  collections  with  B  on  December  12  and  with  A  on  April  17. 

SUMMARY  OF  RESULTS  WITH  RECTAL  INJECTIONS  OF  A  5  PER  CENT 

ALCOHOL  SOLUTION. 

These  results  give  evidence  that  after  the  injection  of  5  per  cent  alcohol 
solutions,  varying  in  quantity  from  200  to  1,000  c.  c.,  alcohol  is  almost 
always  eliminated  in  the  urine.  The  amounts  thus  found  are  extraordina¬ 
rily  small,  it  is  true,  but  it  must  be  remembered  that  the  times  covered  by 
the  urine  collections  were  relatively  short,  being  on  the  average  not  over  3 
or  4  hours  after  the  injection  of  the  alcohol.  They  are,  however,  sufficient 
to  indicate  that  the  alcohol  introduced  has  passed  from  the  rectum  into  the 
blood,  and  a  part  from  the  blood-stream  has  found  its  way  into  the  kidneys, 
and  has  finally  been  eliminated  in  the  urine.  In  general,  the  larger  the 
quantity  of  alcohol  injected,  the  larger  is  the  amount  of  alcohol  eliminated 
in  the  urine  and  the  greater  is  the  concentration.  This  is  not,  however,  a 
universal  rule.  In  some  experiments  in  which  there  was  a  second  collection 
period  in  which  the  urine  obtained  was  wholly  secreted  after  the  alcohol  was 
injected,  the  quantities  were  higher  in  concentration  and  larger  in  quantity 
than  in  the  first  collection,  in  which  the  urine  was  diluted  with  that  secreted 
before  the  injection  began. 

Urine  with  Rectal  Injections  of  a  7.5  per  cent  Alcohol  Solution. 

In  13  experiments  7.5  per  cent  alcohol  solutions  were  introduced  rectally, 
the  urines  collected,  and  alcohol  determinations  made.  The  results  are 
given  in  table  9.  The  subjects  are  the  same  as  for  the  5  per  cent  solutions 
except  that  subject  B  was  not  used.  The  amounts  of  alcohol  solution  intro¬ 
duced  varied  in  volume  from  265  c.  c.  to  810  c.  c.,  and  the  urine  eliminated 


Table  9. — Elimination  and  concentration  of  alcohol  in  urine  over  long  'periods  with  7.5  per  cent  alcohol  solutions  introduced  per  rectum. 


STUDIES  OF  URINE  ELIMINATED. 


41 


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Table  10.  Elimination  and  concentration  of  alcohol  in  urine  over  long  periods  with  10  per  cent  alcohol  solutions  introduced  per  rectum. 


42 


HUMAN  METABOLISM  WITH  ENEMATA 


STUDIES  OF  URINE  ELIMINATED. 


43 


from  167  c.  c.  in  the  second  collection  on  April  15  to  915  c.  c.  on  April  18. 
The  amounts  of  alcohol  eliminated  in  the  urine  ranged  from  0.04  gram  to  0.43 
gram.  In  two  experiments  with  A  (on  April  10  and  the  first  collection  on 
April  15)  the  urine  showed  no  trace  of  alcohol.  The  concentration  of  alco¬ 
hol  in  the  urine  varied  from  0  mg.  to  0.56  mg.  In  general,  the  higher 
values  were  found  in  the  last  6  experiments,  5  of  which  were  with  500  c.  c.  of 
a  7.5  per  cent  alcohol  solution  and  the  urine  collection  extended  over  the 
entire  night,  i.  e.,  beginning  at  7h  30m  p.m.  to  9h  10m  p.m.,  and  ending  at 
7h  05m  a.m.  to  7h  45m  a.m.  The  percentage  of  alcohol  excreted  in  the  urine 
varied  from  0  with  A  on  April  10  to  1.2  per  cent  with  A  on  February  3. 

SUMMARY  OF  RESULTS  WITH  RECTAL  INJECTIONS  OF  A  7.5  PER  CENT 

ALCOHOL  SOLUTION. 

When  7.5  per  cent  alcohol  solutions,  varying  in  volume  from  265  to  810 
c.  c.  were  injected  rectally,  the  urines  voided  in  the  subsequent  2  to  8  hours 
contained  alcohol  ranging  in  quantity  from  0  to  427  mg.,  and  had  an  alcohol 
concentration  from  0  to  0.56  mg.  per  cubic  centimeter  of  urine  and  a 
percentage  elimination  from  0  to  1.2  per  cent.  In  general,  the  percentages 
excreted  with  7.5  per  cent  alcohol  solutions  are  not  materially  higher  than 
those  with  5  per  cent  alcohol  solutions.  The  concentrations  are  slightly 
higher,  particularly  in  those  experiments  when  the  urines  were  collected 
over  a  long  period  during  the  night.  It  must  be  noted,  however,  that  the 
quantity  of  absolute  alcohol  in  this  case  was  37.5  grams,  nearly  50  per  cent 
larger  than  in  the  majority  of  experiments  with  5  per  cent  alcohol  solutions. 

Urine  with  Rectal  Injections  of  a  10  per  cent  Alcohol  Solution. 

In  4  experiments  10  per  cent  alcohol  solutions  were  injected  rectally,  the 
urines  collected,  and  alcohol  determinations  made.  The  results  are  given  in 
table  10.  The  solution  injected  was  265  or  260  c.  c.  in  volume,  containing 
26.5  or  26  grams  of  alcohol.  The  volume  of  urine  collected  varied  from  79 
c.  c.  to  790  c.  c.  The  amount  of  alcohol  in  these  urines  varied  from  0.02  to 
0.12  gram,  the  concentration  from  0.10  to  0.33  milligram,  and  the  percentage 
excretion  from  0.4  to  0.7.  In  general,  the  concentrations  were  slightly 
higher  than  the  concentrations  with  either  5  per  cent  or  7.5  per  cent  alcohol 
solutions  in  the  experiments  of  about  the  same  duration  and  with  about  the 
same  quantities  of  alcohol. 

COMPARISON  OBSERVATIONS  OF  ALCOHOL  IN  URINE  AFTER 

ITS  INGESTION  BY  MOUTH.  * 

In  6  experiments  alcohol  was  given  by  mouth  in  concentrations  of  5,  7.5, 
and  10  per  cent.  In  3,  400  c.  c.  of  a  5  per  cent  solution  were  given,  in  2,  250 
c.  c.  of  a  7.5  per  cent  solution,  and  in  one,  250  c.  c.  of  a  10  per  cent  solution. 
The  urines  were  collected  in  the  same  manner  as  in  the  preceding  experiments, 
and  the  results  of  the  analyses  are  given  in  table  11.  The  volumes  of  urine 
varied  from  70  c.  c.,  the  second  collection  on  December  23,  to  862  c.  c.,  the  first 
collection  for  the  same  date.  The  amount  of  alcohol  in  the  urine  ranged  from 
0.01  gram  to  0.25  gram.  The  concentration  varied  from  0.19  to  0.32  mg., 
so  that,  on  the  average,  the  concentrations  were  a  little  higher  than  those 
with  corresponding  amounts  given  by  rectum.  The  percentage  excretion  of 


Table  11. — Elimination  and  concentration  of  alcohol  in  urine  over  long  periods  with  5,  7.5 ,  and  10  per  cent  solutions  given  hy  mouth. 


44 


HUMAN  METABOLISM  WITH  ENEMATA 


STUDIES  OF  URINE  ELIMINATED. 


45 


alcohol  in  the  urine  varied  from  0.5  to  1.1  per  cent.  The  average  figures 
are  thus  likewise  slightly  higher  than  the  averages  for  the  preceding  groups 
of  urines  when  alcohol  was  given  by  rectum. 

This  comparison  brings  out  the  fact  that  even  when  differing  methods 
were  used  for  introducing  the  alcohol,  namely,  by  rectum  and  by  mouth, 
the  concentration  of  the  alcohol  in  the  urine  collected  over  a  period  of  time 
was  about  the  same  in  both  cases  and  the  amount  of  alcohol  eliminated  in 
the  urine  was  likewise  similar.  This  would  indicate  that  the  rate  of  absorp¬ 
tion  and  the  rate  of  distribution  and  variation  in  concentration  from  time  to 
time  are  not  unlike  with  rectal  and  oral  introduction  of  alcohol.  These 
findings  are  important  in  comparing  the  effects  of  alcohol  introduced  by  dif¬ 
ferent  methods  upon  the  respiratory  exchange,  the  heart-rate,  and  the  total 
metabolism,  which  are  considered  in  discussing  the  results  of  the  metabolism 
experiments. 

ELIMINATION  AND  CONCENTRATION  OF  ALCOHOL  IN 
URINE  AFTER  ITS  RECTAL  INJECTION  (SHORT 
COLLECTION  PERIODS). 

When  alcohol  was  found  in  urine  at  the  end  of  these  long  experimental 
periods  in  which  solutions  were  injected  by  rectum,  it  was  believed  that  the 
determination  of  alcohol  in  urines  collected  at  intervals,  with  periods  as  short 
as  possible,  would  throw  some  light  on  the  metabolism  of  alcohol.  Experi¬ 
ments  were  therefore  carried  out  in  which  this  was  done.  In  most  cases  the 
subject  was  in  a  sitting  position.  Every  15  minutes  he  drank  a  glassful  of 
tap-water  so  as  to  promote  a  free  flow  of  urine.  The  urine  was  voided  by  the 
subject  whenever  possible,  and  consequently  the  lengths  of  the  periods  were 
influenced  by  several  factors,  viz,  the  influence  of  alcohol  itself;  nervous 
mechanism  of  the  subject;  quantity  of  fluid  taken  by  the  mouth;  quantity  of 
fluid  injected  rectally;  and  finally  the  ability  of  the  subject  to  retain  the 
solution  injected  rectally  and  at  the  same  time  relax  the  bladder  sphincter. 
The  last  concerns  most  the  first  collection  of  urine  after  the  rectal  injection 
began  and  proved  to  be  the  most  important  factor  in  determining  the  length 
of  this  period.  A  number  of  times  the  subject  desired  to  urinate,  but  did  not 
do  so  for  fear  of  losing  the  solution  which  had  been  injected. 

The  results  of  the  determinations  of  the  alcohol  in  urine  collected  in  short 
periods  after  rectal  injection  are  presented  and  discussed  in  the  following 
pages.  In  table  12  details  are  given  for  each  experiment  of  the  time  and 
amount  of  the  injection,  times  of  urination,  length  of  periods  of  collection, 
total  volume  of  urine  collected  in  each  period  before  and  after  injection, 
volume  of  urine  per  minute,  the  amount  of  alcohol  eliminated  in  the  urine, 
and  the  concentration,  i.  e.,  the  amount  of  alcohol  per  cubic  centimeter  of 
urine. 

In  all,  there  were  9  experiments,  2  with  subject  A  and  7  with  subject  C. 
In  the  8  experiments  with  a  5  per  cent  solution  of  alcohol,  the  volume  ranged 
between  420  and  500  c.  c.,  except  in  1  experiment,  when  it  was  750  c.  c.  In  the 
remaining  experiment,  250  c.  c.  of  a  10  per  cent  solution  were  injected.  The 
first  collection  of  alcohol  urine  was  from  1  hour  and  5  minutes  to  2  hours  and 
22  minutes  after  the  beginning  of  the  injection,  but  usually  inside  of  2  hours. 


46 


HUMAN  METABOLISM  WITH  ENEMATA. 


As  a  rule,  the  observations  were  continued  for  5  or  6  hours  excluding  those 
overnight.  Detailed  statistics  for  the  experiment  with  A  on  December  15, 
1915,  will  suffice  to  indicate  the  characteristics  of  the  whole  group,  and  a 
more  general  discussion  of  these  experiments  with  short  periods  of  urine 
collection  will  be  given  later. 


Table  12. — Elimination  and  concentration  in  urine  of  alcohol  injected  by  rectum. 


Subject,  date,  and  time 
of  urinating. 

Length 

of 

period. 

Time 

since 

Volume  of  urine. 

Alcohol  excreted 
in  urine. 

alcohol 

injected. 

Total. 

Per 

minute. 

Total. 

Per  c.  c. 
of  urine. 

C.  Dec.  2,  1915. 

min. 

h.  min. 

c.  c. 

c.  c. 

mg. 

mg. 

5h  27 m  p.  m . 

7  40“  . 

420  c.  c. 
170 

of  5  per  ce 
2  13 

nt  solutioi 
118 

a. 

6.9 

12 

0.10 

8  01  . 

21 

2  34 

750 

35.7 

76 

.10 

8  50  . 

49 

3  23 

450  ' 

9.2 

24 

.05 

9  40  . 

50 

4  13 

465 

9.3 

0 

•  •  <  • 

10  20  . 

40 

4  53 

370 

9.3 

0 

•  •  •  • 

11  45  . 

85 

6  18 

280 

3.3 

0 

•  •  •  • 

Dec.  3,  1915. 

7h  25 m  a.  m.6 . 

460 

13  58 

287 

0.6 

0 

.... 

Total . 

c  112 

Average . 

.  . 

0.08 

A.  Dec.  15,  1915. 

4h  43 m  p.  m.“ . 

253 

340 

1.3 

5  IS  to  5h  47m  p.  m. .  . 

6  30  p.  rn . 

450  c.  c. 
107 

of  5  per  ( 
1  12 

jent  soluti 
162 

on. 

1.5 

44 

0.27 

7  00  . 

30 

1  42 

240 

8.0 

76 

.32 

7  28  . 

28 

2  10 

202 

7.2 

54 

.27 

8  05  . 

37 

2  47 

322 

8.7 

64 

.20 

8  51  . 

46 

3  33 

430 

9.3 

52 

.  12 

9  33  . 

42 

4  15 

347 

8.3 

15 

.04 

10  03  . 

30 

4  45 

322 

10.7 

11 

.03 

10  05  . 

2 

4  47 

39 

19.5 

10  46  . 

41 

5  28 

381 

9.3 

0 

.... 

11  50  . 

64 

6  32 

448 

7.0 

0 

Dec.  16,  1915. 

7h  05m  a.  m.6 . 

435 

13  47 

685 

1.6 

Trace 

.... 

Total . 

c316 

Average . 

.... 

0.16 

C.  Dec.  10,  1915. 

5h  00m  p.  m.° . 

150 

140 

0.9 

Trace 

j 

5  20  to  5h  47ra  p.  m. .  .  . 

6  55  p.  m . 

470  c.c.  ( 
115 

)f  5  per  cei 
1  35 

at  solutior 
830 

L. 

7.2 

137 

0.16 

7  25  . 

30 

2  5 

285 

9.5 

53 

.18 

8  55  . 

90 

3  35 

575 

6.4 

80 

.14 

9  50  . 

55 

4  30 

295 

5.4 

13 

.04 

9  55  . 

5 

4  35 

97 

19.4 

3 

.03 

10  25  . 

30 

5  5 

330 

11.0 

0 

.... 

11  40  . 

75 

6  20 

540 

7.2 

0 

.... 

Dec.  11,  1915. 

7h  15ra  a.  m.6 . 

455 

13  55 

360 

0.8 

Trace 

.... 

Total . 

c  286 

Average . 

.  . 

.... 

0.14 

STUDIES  OF  URINE  ELIMINATED. 


47 


Table  12. 


— Elimination  and  concentration  in  urine  of  alcohol  injected  by  rectum — Cont. 


Subject,  date,  and  time 
of  urinating. 

Length 

of 

period. 

Time 

since 

alcohol 

injected. 

Volume  of  urine. 

Alcohol  excreted 
in  urine. 

Total. 

Per 

minute. 

Total. 

Per  c.  c. 
of  urine. 

Dec.  10,  1915. 

min. 

h. 

min. 

c.  c. 

c.  c. 

mg. 

mg. 

6h 

00m 

p.  m.° . 

180 

,  . 

435 

2.4 

Trace 

.... 

5 

20 

to  5h  39m  p.  m. 

470  c.  c 

of  5 

per 

cent  solution. 

6 

36 

p.  m . 

96 

1 

16 

485 

5.1 

112 

0.23 

7 

25 

49 

2 

5 

370 

7.6 

99 

.27 

8 

25 

60 

3 

5 

495 

8.3 

87 

.18 

9 

30 

65 

4 

10 

565 

8.7 

35 

.06 

10 

00 

30 

4 

40 

318 

10.6 

6 

.02 

10 

25 

25 

5 

5 

220 

8.8 

0 

.... 

Total . 

e339 

Average . 

.... 

.  .  . 

0.15 

Dec.  17,  1915. 

5h 

00m 

p.  m.a . 

270 

,  , 

518 

1.9 

Trace 

.... 

5 

18 

500  c.  c. 

of  5 

per  cent  solution. 

7 

40 

160 

2 

22 

570 

3.6 

92 

0.16 

8 

40 

60 

3 

22 

498 

8.3 

69 

.14 

9 

12 

32 

3 

54 

190 

5.9 

11 

.06 

9 

45 

33 

4 

27 

250 

7.6 

9 

.04 

10 

10 

25 

4 

52 

290 

11.6 

8 

.03 

12 

00 

110 

6 

42 

1087 

9.9 

0 

.... 

Dec.  18,  1915. 

7h 

30m 

a.  m.b . 

450 

14 

12 

655 

1.5 

Trace 

.... 

Total . 

c  189 

Average . 

.... 

0.11 

Dec.  20,  1915. 

? 

•  •  • 

,  . 

,  , 

79 

•  •  •  • 

0 

.... 

6h 

10m 

p.  m . 

... 

,  . 

,  , 

138 

.... 

<*25 

0.18 

6 

25 

15 

.  . 

192 

12.8 

0 

.... 

6 

27 

to  6h  49m  p.  m.  .  . 

500  c.  c. 

of  5 

per  cent  solution. 

8 

30 

p.  m . 

125 

2 

3 

1130 

9.0 

140 

.12 

9 

25 

55 

2 

58 

415 

7.5 

38 

.09 

9 

50 

25 

3 

23 

300 

12.0 

15 

.05 

11 

05 

75 

4 

38 

614 

8.2 

15 

.03 

Dec.  21,  1915. 

7h 

30m 

505 

13 

3 

614 

1.2 

Trace 

.... 

Total . 

Average . 

.  . 

. .  . 

.... 

c208 

0.08 

48 


HUMAN  METABOLISM  WITH  ENEMATA. 


Table  12. — Elimination  and  concentration  in  urine  of  alcohol  injected  hy  rectum — Cont. 


Subject,  date,  and  time 
of  urinating. 

Length 

of 

period. 

Time 

since 

alcohol 

injected. 

Volume  of  urine. 

Alcohol  excreted 
in  urine. 

Total. 

Per 

minute. 

Total. 

Per  c.  c. 
of  urine. 

Jan.  15,  1916. 

min. 

h. 

min. 

c.  c. 

c.  c. 

mg. 

mg. 

lh 

55m  p.  m.° . 

325 

.  . 

,  . 

348 

1.1 

0 

•  •  •  • 

2 

16  to  2h  21m  p.  m. .  .  . 

500  c.  c. 

of  5  per  cent  solution. 

3 

21  p.  m . 

86 

1 

5 

325 

3.8 

80 

0.25 

3 

55  . 

34 

1 

39 

260 

7.6 

60 

.23 

4 

25  . 

30 

2 

9 

290 

9.7 

48 

.16 

4 

45  . 

20 

2 

29 

235 

11.7 

23 

.10 

6 

15  . 

30 

2 

59 

270 

9.0 

16 

.06 

5 

45  . 

30 

3 

29 

370 

12.3 

10 

.03 

Total . 

e237 

Average . 

•  •  •  • 

. . . 

0.14 

Jan.  18,  1916. 

2h 

13m  to  2h  35m  p.  m . 

750  c.  c. 

of  5  per  cent  solution. 

4 

05  p.  m.° . 

120 

1 

52 

550 

4.6 

190 

0.35 

5 

15  . 

70 

3 

2 

550 

7.9 

152 

.28 

6 

00  . 

45 

3 

47 

425 

9.4 

116 

.27 

7 

00  . 

60 

4 

47 

620 

10.3 

115 

.19 

8 

06  . 

66 

5 

53 

665 

10.1 

91 

.14 

9 

00  . 

54 

6 

47 

660 

12.2 

30 

.05 

Total . 

•  •  • 

e  694 

Average . 

. . . 

•  • 

•  •  • 

.... 

•  •  • 

6.20 

May  6 

1916. 

lh 

45m  p.  m.° . 

75 

#  # 

73 

1.0 

Trace 

•  •  •  • 

2 

00  to  2h  04m  p.  m.  .  . 

250  c.  c. 

of  10 

per  cent  solul 

don. 

3 

40  p.  m . 

115 

1 

40 

445 

8.1 

159 

0.36 

4 

15  . 

35 

2 

15 

70 

2.0 

20 

.28 

4 

53  . 

38 

2 

53 

197 

5.2 

31 

.16 

5 

50  . 

57 

3 

50 

169 

3.0 

24 

.14 

6 

15  . 

25 

4 

15 

35 

1.4 

Lost 

•  •  •  • 

6 

45  . 

30 

4 

45 

204 

6.8 

9 

.04 

7 

12  . 

27 

5 

12 

255 

9.5 

9 

.04 

7 

55  . 

43 

5 

55 

94 

2.2 

3 

.04 

Total . 

•  •  • 

•  •  •  • 

c255 

Average . 

•  •  • 

•  • 

•  • 

•  •  • 

•  •  •  • 

•  .  • 

0.18 

°  Urine  passed  before  experiment,  but  not  saved,  at  the  following  times:  Dec.  2,  4h  50m  p.m.;  C, 
Dec.  10,  2h  30m  p.  m. ;  A,  Dec.  10,  2  p.  m. ;  Dec.  15  and  17, 12h  30m  p.  m. ;  Jan.  15,  8h  30m  a.  m. ; 

Jan.  18,  2h  05m  p.  m.;  May  6,  12h  30m  p.  m. 
b  Collected  by  subject. 

‘The  proportional  part  of  the  alcohol  injected  which  was  eliminated  in  the  urine  was  as  follows: 
Dec.  2,  0.6  p.  ct.;  C,  Dec.  10,  1.3  p.  ct. ;  A,  Dec.  10,  1.5  p.  ct.;  Dec.  15,  1.4  p.  ct. ;  Dec.  17, 

0.8  p.  ct. ;  Dec.  20,  0.9  p.  ct. ;  Jan.  15,  1.0  p.  ct. ;  Jan.  18,  1.9  p.  ct. ;  May  6,  1.1  p.  ct. 

d  Presumably  due  to  taking  of  coffee.  (See  p.  58.) 


SUBJECT  G  DEC.  2.  1915 

420  00.  5  PERCENT  ALCOHOL,  Ga  Mgm  SUBJECT  C.  DEC  1071915 


STUDIES  OF  URINE  ELIMINATED 


49 


i-2  om  o  moino 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN  HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 

Fig.  1.— Milligrams  of  alcohol  per  cubic  centimeter  of  urine,  and  volume  of  urine  per  minute,  after  rectal  injection  of  420  to  470  c.  c.  of  a  5  per  cent  (by  weight)  alcohol  solution. 


50 


HUMAN  METABOLISM  WITH  ENEMATA. 


Subject  A,  December  15,  1915. — Rectal  injection,  450  c.  c.  of  a  5  per  cent 
alcohol  solution.  The  injection  was  given  between  5h  18m  and  5h  47m  p.  m. 
and  the  urine  was  collected  thereafter  at  short  intervals.  The  first  col¬ 
lection  after  the  alcohol  was  at  6h  30m  p.  m.  or  1  hour  and  12  minutes  after 
the  solution  had  been  given;  the  alcohol  concentration  of  the  urine  was  0.27 
mg.  per  cubic  centimeter.  The  urine  collected  in  the  second  period,  ending 
at  7  p.  m.,  1  hour  and  42  minutes  after  the  beginning  of  the  injection,  gave 
the  highest  concentration  for  this  day,  i.  e.,  0.32  mg.  per  cubic  centimeter. 


C  C.  Mgm  SUBJECT  C  DEC.  17.  1915 


C.c.  Mgm  SUBJECT  C.  DEC.  20.  1915 


C  c  Mgm  SUBJECT  C.  JAN  15.  1916 


Fig.  2. — Milligrams  of  alcohol  per  cubic  centimeter  of  urine,  and  volume  of  urine  per 
minute,  after  rectal  injection  of  500  c.  c.  of  a  5  per  cent  (by  weight)  alcohol 
solution. 


STUDIES  OF  URINE  ELIMINATED. 


51 


No  alcohol  was  found  at  10h  05m  p.  m.  (4  hours  and  47  minutes  after  the 
injection  began),  and  there  was  none  obtained  subsequently,  except  for  a 
possible  trace  in  the  urine  collected  by  the  subject  the  following  morning. 
The  average  concentration  was  0.16  mg.  per  cubic  centimeter,  while  the 
total  alcohol  eliminated  in  the  urine  was  316  mg.,  or  1.4  per  cent  of  the  total 
amount  of  alcohol  injected. 

The  results  of  these  experiments  are  also  expressed  graphically  by  means  of 
charts.  (See  figs.  1  to  3.)  In  these  curves  the  milligrams  of  alcohol  per  cubic 
centimeter  of  urine  are  plotted  at  the  middle  of  the  period  this  point  being 


C.  c.  Mgm  SUBJECT  C  JAN.  ia  1916 


C.  c.  Mgm  SUBJECT  C  MAY  6.  1916 


Fig.  3. — Milligrams  of  alcohol  per  cubic  centimeter  of  urine,  and  volume  of  urine  per  minute,  after  rectal 
injection  of  750  c.  c.  of  a  5  per  cent  (by  weight)  alcohol  solution,  and  250  c.  c.  of  a  10  per  cent  (by 
weight)  a  cohol  solution. 


52 


HUMAN  METABOLISM  WITH  ENEMATA. 


considered  to  give  an  average  for  that  period,  not  a  concentration  at  a  single  point 
of  time.  The  average  volume  per  minute  is  plotted  by  the  “  block  ”  method, 
that  is,  the  horizontal  line  represents  the  whole  period  and  the  vertical  lines 
indicate  the  ends  of  the  periods.  In  presenting  the  results  in  the  tables  and 
charts,  the  experiments  are  arranged  first,  according  to  the  percentage  of 
alcohol  in  the  solution,  and  second,  according  to  the  volumes  of  the  alcohol 
solutions  injected. 

COMPARISON  EXPERIMENTS  WITH  URINE  COLLECTED 
AT  SHORT  INTERVALS  AFTER  INGESTION  OF 
ALCOHOL  SOLUTIONS  BY  MOUTH. 

In  addition  to  these  experiments  with  rectal  injection,  it  was  thought 
desirable  to  have  comparison  experiments  in  which  the  urine  was  likewise 
collected  at  short  intervals,  but  the  alcohol  solution  was  given  by  mouth.1 
In  the  experiments  here  recorded  the  subjects  passed  urine,  then  immediately 
took  the  alcohol  in  water,  drinking  it  as  quickly  as  possible.  The  data  for 
the  experiments  are  given  in  table  13  and  in  figure  4,  the  method  of  presenta¬ 
tion  being  the  same  as  for  the  experiments  in  which  the  solutions  were  given 
rectally. 

There  were  4  experiments  in  all,  2  each  with  subjects  A  and  C.  In  the 
first  3,  25  grams  of  alcohol  were  given  by  mouth  in  a  5  per  cent  alcohol  solu¬ 
tion,  and  in  the  final  experiment  the  same  amount  was  given  in  a  10  per  cent 
solution.  In  all  but  one  of  the  group  the  first  collection  of  urine  was  earlier 
than  in  the  rectal  experiments,  being  but  45  or  27  minutes  after  the  injection 
began,  but  the  observations  were  not  usually  made  over  so  long  a  period,  and 
in  but  one  case  did  the  alcohol  entirely  disappear  from  the  urine.  As  with 
the  rectal  experiments,  the  highest  concentration  was  found  in  the  first  or 
second  sample  of  urine,  and  always  within  2  hours.  The  results  of  the  rectal 
and  mouth  experiments  will  be  compared  in  the  general  discussion  of  these 
short-period  observations. 

DISCUSSION  OF  THE  RESULTS  OBTAINED  WITH  SHORT 
PERIODS  OF  URINE  COLLECTION. 

The  collection  of  the  urine  in  short  periods  after  giving  by  rectum  and  by 
mouth  alcohol  solutions  with  concentrations  of  5  and  10  per  cent  has  brought 
out  several  features.  In  the  first  place,  there  was  a  very  distinct  peak,  that 
is,  a  point  of  time  at  which  the  highest  concentration  was  obtained.  An 
examination  of  the  several  charts  shows  that  this  peak  occurred  in  every  in¬ 
stance  within  the  first  2  hours,  and  in  the  first  or  second  collection  period. 
Unfortunately,  in  many  of  the  rectal  experiments,  the  first  collection  of  urine 
did  not  follow  so  soon  after  the  introduction  of  alcohol  as  might  be  desired, 
although  theoretically  it  should  be  possible  to  obtain  these  collections  in  ex¬ 
tremely  short  periods,  as  Widmark  has  done.2  It  is  therefore  quite  likely 
that  the  actual  peak  sometimes  occurred  even  earlier  than  was  found. 

*A  more  intensive  study  of  this  character  has  since  been  carried  out  in  this  Laboratory  by  Miles, 

and  published.  (Miles:  Journ.  Pharm.  and  Exp.  Therapeutics,  1922,  20,  p.  265,  Ibid.,  Carnegie 

Inst.  Wash.  Pub.  No.  333,  1924,  pp.  211  to  222.) 

2  Widmark:  Skand.  Arch.  f.  Physiol.,  1916,  33,  p.  85. 


STUDIES  OF  URINE  ELIMINATED 


53 


Table  13. — Elimination  and  concentration  in  urine  of  alcohol  ingested  by  mouth. 


Subject,  date,  and  time 
of  urinating. 

Length 

of 

period. 

Time 

since 

alcohol 

ingested. 

Volume  of 
urine. 

Alcohol  excreted 
in  urine. 

Total. 

Per 

min. 

Total. 

Per  c.  c. 
of  urine. 

Jan.  8, 

1916: 

min. 

h.  min. 

c.  c. 

c.  c. 

mg. 

mg. 

lh 

45m  p.  m.° . 

330 

,  , 

,  , 

227 

0.7 

... 

.... 

1 

50  to  lh  53m  p.  m.. . 

500  c.  c. 

of  5 

p.  ct.  solution. 

2 

35  p.  m . 

50 

0 

45 

42 

.8 

13 

0.31 

3 

18  . 

43 

1 

28 

310 

7.2 

83 

.27 

3 

54  . 

36 

2 

4 

355 

9.9 

74 

.21 

4 

35  . 

41 

2 

45 

412 

10.0 

73 

.18 

5 

18  . 

43 

3 

28 

463 

10.8 

43 

.09 

5 

58  . 

40 

4 

8 

542 

13.6 

24 

.05 

Total . 

b310 

Average . 

. . . 

.... 

. . . 

0.15 

Jan.  8,  1916: 

lh 

45m  p.  m.® . 

705 

.  , 

.  # 

320 

0.5 

... 

.... 

1 

50  to  lh  53m  p.  m. .  . 

500  c.  c. 

of  5 

p.  ct.  solution. 

2 

35  p.  m . 

50 

0 

45 

71 

1.4 

23 

0.33 

3 

17  . 

42 

1 

27 

345 

8.2 

132 

.38 

3 

53  . 

36 

2 

3 

405 

11.2 

134 

.33 

4 

35  . 

42 

2 

45 

437 

10.4 

102 

.23 

5 

17  . 

42 

3 

27 

442 

10.5 

65 

.15 

5 

57  . 

40 

4 

7 

480 

12.0 

28 

.06 

Total . 

&484 

Average . 

. . . 

.... 

0.22 

Jan.  12,  1916: 

4h 

45m  p.  m.° . 

195 

#  # 

90 

0.5 

•  .  • 

.... 

4 

50  . 

500  c.  c. 

of  5  p.  ct.  solution. 

6 

45  . 

120 

1 

55 

363 

3.0 

120 

0.33 

7 

45  . 

60 

2 

55 

417 

7.0 

85 

.20 

8 

47  . 

62 

3 

57 

462 

7.5 

40 

.10 

9 

26  . 

39 

4 

36 

316 

8.1 

10 

.03 

9 

55  . 

29 

5 

5 

235 

8.1 

Trace 

•  «  .  . 

10 

32  . 

37 

5 

42 

245 

6.6 

0 

.... 

Total . 

b255 

.... 

Average . 

.... 

0.16 

Apr.  20,  1916: 

12h 

32 m  p.  m.® . 

212 

,  , 

149 

0.7 

... 

.... 

12 

33  to  12h36mp.rn..  . 

250  c.  c. 

of  10  p.  ct.  solution. 

1 

00  p.  m . 

28 

0 

27 

44 

1.6 

7 

0.16 

1 

35  . 

35 

1 

2 

295 

8.4 

113 

.38 

2 

13  . 

38 

1 

40 

250 

6.6 

74 

.30 

2 

50  . 

37 

2 

17 

295 

8.0 

58 

.20 

3 

43  . 

53 

3 

10 

200 

3.8 

31 

.15 

4 

25  . 

42 

3 

52 

136 

3.2 

10 

.08 

5 

20  . 

55 

4 

47 

289 

5.3 

14 

.05 

5 

52  . 

32 

5 

19 

228 

7.1 

7 

.03 

6 

28  . 

36 

5 

55 

220 

6. 1 

6 

.03 

6 

55  . 

27 

6 

22 

73 

2.7 

2 

.03 

Total . 

•  •  • 

•  •  • 

.... 

b  323 

Average . 

•  •  • 

•  • 

•  •  • 

.... 

•  •  • 

0.15 

°  Urine  passed  before  the  experiment,  but  not  saved,  at  the  following  times:  C,  Jan.  8,  8h  15m 
a.  m.;  A,  Jan.  8,  7  a.  m;  Jan.  12,  lh  30m  p.  m. ;  Apr.  20,  9  a.  m. 

6  The  proportional  part  of  the  alcohol  injected  which  was  eliminated  in  the  urine  was  as  follows:  C, 
Jan.  8,  1.2  p.  ct.;  A,  Jan.  8,  1.9  p.  ct.;  Jan.  12,  1  p.  ct. ;  Apr.  20,  1.3  p.  ct. 


54 


HUMAN  METABOLISM  WITH  ENEMATA 


•§ 

09 

a 

o 

o 

M 

0> 

a 

10 


o 

A 

o 

o 


09 

l-i 

M 

lO 

(N 


O 

5 

0) 

s 


a 

o 

o 


o 

•  H 

J3 

3 

O 


(4 

0) 

a 


o 

-a 

o 

o 

09 


•4H 

o 


co 

a 

09 

M 

m 

3 


6 

M 


STUDIES  OF  URINE  ELIMINATED. 


55 


There  were  several  instances  in  the  mouth  experiments  in  which  the  first 
collection  was  made  within  an  hour,  and  in  nearly  all  of  both  groups  of  ex¬ 
periments  the  first  alcohol  urine  was  obtained  within  2  hours.  When  the 
volume  of  alcohol  introduced  was  below  500  c.  c.  of  a  5  per  cent  solution  (less 
than  25  grams  by  weight),  the  alcohol  concentration  of  the  urine  collected  in 
the  second  period  was  the  same  or  higher  than  that  of  the  first  period,  that  is, 
the  peak  occurred  in  the  second  hour.  (See  fig.  1.)  On  the  other  hand, 
when  the  volume  of  the  5  per  cent  solution  was  500  c.  c.  and  over,  or  a  10  per 
cent  solution  was  used,  i.  e.,  25  or  more  grams  of  alcohol,  the  sample  col¬ 
lected  in  the  first  period  had  the  maximum  concentration,  the  peak  occurring 
in  or  near  the  first  hour  when  the  first  collection  was  early  enough  to  show  the 
probable  true  maximum.  This  is  also  true  of  all  the  mouth  experiments,  ex¬ 
cept  possibly  that  with  A  on  January  8.  In  the  mouth  experiment  on  April 
20,  the  first  collection  period  was  but  27  minutes  long,  and  accordingly  the 
maximum  concentration  did  not  occur  until  the  second  period,  ending  1  hour 
and  2  minutes  after  the  beginning  of  the  injection. 

The  concentration  of  alcohol  in  the  urine  can  be  taken  as  an  indication  of 
the  actual  content  of  alcohol  in  the  body,  or  rather  of  the  changes  in  its  con¬ 
centration  in  the  body.  In  the  earlier  part  of  the  experiment,  at  least,  the 
alcohol  concentration  in  the  urine  must  represent  the  balance  between  the 
absorption  and  the  utilization  of  the  amount  injected,  for  if  we  have  a  curve 
in  which  successive  samples  of  urine  show  higher  concentrations  of  alcohol, 
we  must  believe  that  the  absorption  is  taking  place  more  rapidly  than  the 
utilization  or  disappearance.  Since  with  an  injection  of  25  grams  of  alcohol 
or  over,  the  urine  collected  in  the  first  hour  had  the  maximum  concentration, 
it  is  apparent  that  the  higher  the  alcohol-content  of  the  solution,  the  more 
quickly  is  the  peak  of  concentration  in  the  body  reached.  In  other  words, 
the  time  the  peak  occurs  is  dependent  upon  the  amount  of  alcohol  introduced. 
A  comparison  of  the  two  rectal  experiments  of  January  18  and  May  6,  with 
the  same  subject  and  with  the  length  of  the  first  collection  period  approxi¬ 
mately  the  same,  indicates  that  the  concentration  of  the  alcohol  in  the  solu¬ 
tion  injected  may  also  have  a  bearing  upon  the  time  of  maximum  concentra¬ 
tion  in  the  urine  eliminated,  for  although  in  the  experiment  with  the  10  per 
cent  solution  but  25  grams  of  alcohol  were  injected,  as  compared  with  37.5 
grams  in  the  experiment  with  the  5  per  cent  solution,  the  concentration  in  the 
urine  reached  the  peak  at  apparently  about  the  same  time  as  indicated  by  the 
amount  of  concentration. 

The  time  of  disappearance  of  alcohol  from  the  urine  after  the  occurrence  of 
the  peak  was  not  determined  in  all  cases,  as  the  observations  were  not  always 
of  sufficient  length.  In  the  first  5  experiments  with  rectal  injection,  the  last 
urine  collections  contained  no  alcohol;  consequently  these  observations  were 
continued  to  a  point  when  the  alcohol  elimination  had  ceased.  With  possi¬ 
bly  one  exception  (the  experiment  of  December  17  with  C),  the  time  covered 
by  the  total  alcohol  elimination  in  these  5  experiments  was  under  5  hours. 
The  conclusion  may  therefore  be  drawn  that  25  grams  of  alcohol  taken  in 
the  form  of  a  5  per  cent  solution,  introduced  rectally,  disappears  completely 
from  the  urine,  and  therefore  presumably  from  the  blood,  within  5  hours. 
The  experiments  of  December  20  and  January  15  may  also  be  considered  as 
confirming  this  conclusion,  for  although  the  observations  in  short  periods 
were  not  continued  for  a  full  5  hours,  yet  the  alcohol  in  the  urine  in  the  last 
observation  in  each  experiment  was  near  the  vanishing-point. 


56 


HUMAN  METABOLISM  WITH  ENEMATA. 


The  falling  off  in  the  concentration  was  less  rapid  than  the  rise  in  the  be¬ 
ginning  of  the  experiment,  for  as  the  absorption  was  ended  and  apparently  a 
large  amount  of  the  alcohol  had  already  been  burned  or  utilized,  there  was 
less  alcohol  to  burn,  even  at  the  peak  of  absorption,  and  consequently  it  dis¬ 
appeared  at  a  slower  rate. 

In  the  experiment  in  which  750  c.  c.  of  a  5  per  cent  alcohol  solution  were 
given  (January  18),  the  time  of  disappearance  of  alcohol  from  the  urine  was 
somewhat  later  than  in  the  earlier  experiments,  in  which  the  volume  of  the 
solution  and  amount  of  alcohol  were  less.  Notwithstanding  the  fact  that 
the  experiment  on  January  18  was  continued  for  nearly  7  hours  after  the  in¬ 
jection,  the  alcohol  did  not  completely  disappear  from  the  urine.  In  the 
experiment  in  which  250  c.  c.  of  a  10  per  cent  solution  were  given  (May  6), 
with  a  smaller  content  of  alcohol  than  in  the  preceding  experiment,  the  result 
was  apparently  of  the  same  order  as  with  750  c.  c.  of  the  5  per  cent  solution, 
for  at  the  end  of  6  hours  there  was  still  a  recognizable  amount  of  alcohol  in  the 
urine. 

The  actual  concentration  of  alcohol  in  the  urine  in  the  9  rectal  experi¬ 
ments  varied  from  0.02  mg.  to  0.36  mg.  per  cubic  centimeter  of  urine.  The 
last  value  was  obtained  in  the  experiment  with  250  c.  c.  of  a  10  per  cent 
solution,  but  nearly  the  same  concentration  (0.35  mg.)  was  obtained  in  the 
experiment  with  750  c.  c.  of  a  5  per  cent  alcohol  solution,  i.  e.,  37.5  grams  of 
alcohol. 

There  was  a  slight  tendency  for  the  higher  amounts  of  alcohol  to  give  a 
higher  absolute  maximum,  but  the  body-weight  of  the  two  subjects  must  be 
taken  into  consideration  in  determining  this  point.  The  body-weight  of  C 
was  about  70  kg.,  while  that  of  A  was  54  kg.  Accordingly,  we  would  expect 
that  with  the  same  amount  of  alcohol,  the  concentration  with  subject  C 
would  be  lower  than  that  with  subject  A.  This  was  apparently  true,  for 
subject  C  with  470  c.  c.  of  a  5  per  cent  solution  had  a  maximum  concentration 
of  0.18  mg.,  while  subject  A,  with  the  some  amount  of  alcohol,  had  a  maxi¬ 
mum  of  0.27  mg.  Unfortunately,  all  of  the  remaining  observations  were 
with  subject  C,  with  whom  there  was  a  variation  in  the  maxima,  for  in 
experiments  with  500  c.  c.  of  a  5  per  cent  solution,  they  ranged  from  0.12  to 
0.25.  In  the  last  two  experiments  with  C,  the  amounts  of  alcohol  given  were 
37.5  grams  and  25  grams,  the  first  in  a  5  per  cent  solution,  and  the  second  in 
a  10  per  cent  solution.  In  each  of  these  experiments  the  maxima  were 
somewhat  higher,  namely,  0.35  and  0.36  mg. 

The  experiments  in  which  the  alcohol  was  introduced  by  mouth  may  also 
be  discussed.  The  collection  of  urine  was  not  so  complicated  in  these 
experiments  as  in  those  with  rectal  injection,  and  in  3  out  of  4  instances  a 
fairly  early  collection  of  urine  was  obtained — from  27  to  45  minutes  after  the 
alcohol  was  taken.  The  time  of  occurrence  of  the  maximum  or  peak  of  the 
concentration  of  alcohol  in  the  urine  has  already  been  discussed  in  the  con¬ 
sideration  of  the  rectal  experiments  in  this  series.  (See  p.  55.)  While  it  is 
somewhat  difficult  to  compare  the  two  groups  of  rectal  and  mouth  experi¬ 
ments  as  to  the  time  the  peak  occurred,  apparently  when  the  alcohol  was 
directly  introduced  by  mouth  the  maximal  concentration  was  obtained  but 
little  before  that  in  the  experiments  when  the  alcohol  was  introduced  rectally, 
certainly  not  more  than  one-half  hour  earlier. 

The  maximal  concentration  of  alcohol  in  the  urine  in  the  4  mouth  experi- 


STUDIES  OF  URINE  ELIMINATED. 


57 


ments  ranged  between  0.38  mg.  and  0.31  mg.  per  cubic  centimeter  of  urine, 
the  average  maxima  being  materially  higher  than  those  in  the  experiments 
with  alcohol  introduced  by  rectum,  even  when  we  compare  the  experiments 
in  which  the  amount  and  concentration  in  solution  were  the  same,  i.  e.,  25 
grams  in  a  5  per  cent  solution.  In  all  probability,  the  higher  maxima  in  the 
mouth  experiments  were  not  due  to  the  delayed  collection  of  the  urines  in  the 
rectal  experiments,  but  either  to  a  more  rapid  absorption,  that  is,  the  alcohol 
reached  the  blood  more  quickly,  or  to  a  slower  utilization  of  the  alcohol  when 
it  was  introduced  by  mouth,  so  that  the  maximal  concentration  in  the  urine 
rose  to  a  higher  point  than  with  rectal  injection.  Owing  to  the  length  of  the 
absorption  experiments  (2  to  6  hours),  we  have  no  measure  of  the  rate  of 
absorption  of  this  quantity  of  alcohol  introduced  by  rectum  except  in  one 
comparatively  short  experiment,  in  which  it  was  found  that,  after  1  hour, 
nearly  all  of  the  alcohol  had  been  absorbed.  (See  experiment  with  A, 
April  10,  table  3,  p.  29.)  From  this  one  experiment  it  would  appear  that 
the  absorption  of  alcohol  introduced  rectally  is  very  rapid,  and  presumably 
almost  as  rapid  as  when  alcohol  is  introduced  by  mouth. 

The  time  that  the  alcohol  disappeared  from  the  urine  was  ascertained  in 
only  one  of  the  mouth  experiments,  that  with  subject  A,  January  12,  and  on 
this  date  it  was  at  the  end  of  5  hours.  (See  table  13.)  It  would  appear 
from  the  shape  of  the  concentration  curves  for  the  4  mouth  experiments  with 
alcohol  (fig.  4)  that  it  did  not  disappear  quite  so  rapidly  from  the  body  or, 
more  accurately,  from  the  urine  itself,  as  when  introduced  rectally.  This 
would  lead  to  the  conclusion  that  the  rapidity  of  utilization  or  disappearance 
of  alcohol  from  the  urine  is  not  so  great  when  it  is  ingested  by  mouth  as  when 
the  introduction  is  rectal.  It  must  be  admitted  that  the  number  and  com¬ 
pleteness  of  the  experiments  are  not  sufficient  to  warrant  the  drawing  of  this 
conclusion  without  some  reserve,  but  the  data  are  fairly  consistent  and 
should  be  taken  into  consideration  in  comparing  the  effect  of  alcohol  when 
introduced  into  the  body  by  these  two  methods.  This  phase  of  the  problem 
will  be  fully  discussed  in  connection  with  the  respiratory  exchange  and  heart- 
rate.  (See  p.139.) 

In  these  experiments  with  ingestion  by  mouth,  we  also  have  a  confirmation 
of  the  statement  of  Widmark  1  and  of  Miles  2  to  the  effect  that  the  diuresis 
has  no  effect  upon  the  actual  concentration.  In  other  words,  in  spite  of 
the  greater  quantity  of  urine  eliminated  in  the  later  periods  of  the  experi¬ 
ments,  there  is  no  parallelism  between  the  dilution  of  urine  and  the  alcohol 
concentration.  At  first  glance  it  would  seem  as  if  there  were  such  a  con¬ 
nection,  because  in  many  experiments  the  curve  for  the  urine  elimination 
per  minute  and  that  for  the  concentration  per  cubic  centimeter  of  urine  are 
reciprocal,  but  there  is  no  regularity  about  this  relationship,  as  there  are  a 
number  of  experiments  in  which  the  amount  of  urine  eliminated  per  minute 
does  not  vary  from  period  to  period,  while  the  concentration  curve  shows  a 
sharp  upward  movement  and  a  more  gradual  descent. 

The  percentage  of  the  total  amount  of  alcohol  introduced  which  was 
eliminated  in  the  urine  varied  in  the  mouth  experiments  from  1.0  to  1.9. 
In  general  the  percentages  were  significantly  higher  than  those  in  experi- 


1  Widmark:  Skand.  Arch.  f.  Physiol.,  1916,  33,  p.  85. 

2  Miles:  Journ.  Pharm.  and  Exp.  Therapeutics,  1922,  20,  p.  265;  Ibid.,  Carnegie  Inst.  Wash.  Pub. 

No.  333,  1924,  p.  138. 


58 


HUMAN  METABOLISM  WITH  ENEMATA. 


merits  previously  discussed  (see  tables  8,  9,  10,  and  11),  in  which  only 
one  or  two  collections  of  urine  were  made.  This  was  due  to  the  larger 
amount  of  urine  eliminated.  Other  things  being  equal,  the  larger  the 
amount  of  urine  eliminated  after  the  taking  of  alcohol,  the  greater  will  be 
the  percentage  of  elimination  of  alcohol.  However,  unlimited  drinking  of 
water  or  other  liquid  would  be  required  to  produce  a  significant  effect  upon 
the  elimination  of  alcohol  in  the  urine  and  its  disappearance  from  the  sys¬ 
tem.  The  fact  must  be  noted,  also,  that  in  the  earlier  series  the  periods  of 
observations  were  not  sufficiently  extended  to  insure  the  total  collection  of 
the  alcohol  eliminated,  since  they  did  not  reach  a  point  when  alcohol  was 
absent  from  the  urine.  These  two  groups  of  experiments  were  not  suf¬ 
ficiently  extensive  to  bring  out  any  difference  in  the  two  individuals  as  to 
the  rate  of  disappearance  of  the  alcohol. 

Observations  are  needed  to  ascertain  whether  this  method  would  be 
satisfactory  for  a  comparison  of  subjects  who  absorb  alcohol  rapidly  with 
those  who  lack  so  great  a  power  of  utilization. 

EFFECT  OF  COFFEE  DRINKING  ON  ELIMINATION  OF  A 

REDUCING  SUBSTANCE. 

On  December  20,  subject  C  drank  clear  coffee  before  the  alcohol  was 
injected  in  order  to  promote  a  freer  flow  of  urine,  i.  e.,  diuresis.  A  collection 
of  urine  was  made  at  6h  10m  p.  m.  and  a  determination  of  alcohol  (i.  e., 
potassium-bichromate  reduction)  was  made;  the  amount  of  bichromate 
reduced  corresponded  to  25  mg.  of  alcohol.  A  similar  determination  was 
made  for  a  sample  collected  at  6h  25m  p.  m.,  which  showed  no  reducing 
power  for  the  potassium  bichromate.  It  has  since  been  substantiated  that 
the  ingestion  of  coffee  extract  will  result  in  a  urinary  excretion  of  a  substance 
capable  of  reducing  potassium  bichromate. 

CONJUGATED  ALCOHOL. 

The  occurrence  of  alcohol  in  the  urine  in  a  conjugated  state  has  been 
reported  by  Neubauer  1  in  an  extensive  investigation  with  compounds  of 
the  fatty-acid  series  upon  the  pairing  of  substances  with  glucuronic  acid  and 
elimination  in  the  urine.  He  gave  ethyl  alcohol  to  2  rabbits  and  2  dogs  and 
proved  the  occurrence  of  glucuronic  acid  in  the  urine  by  polarization  and  by 
difference  in  reduction  before  and  after  hydrolysis.  In  one  case  he  distilled 
the  urine  after  hydrolysis  and  found  the  iodoform  test  to  be  positive  and 
also  determined  the  presence  of  acetaldehyde  after  heating  with  potassium 
bichromate  and  sulphuric  acid.  The  urine  of  the  two  rabbits  gave  relatively 
the  same  amount  of  levo-rotation,  but  with  one  dog  the  evidence  was  inde¬ 
cisive,  while  with  the  other  it  was  positive.  He  reports  no  values  for  the 
quantity  of  alcohol  eliminated  in  this  manner. 

In  the  series  of  determinations  of  alcohol  in  urine  included  in  the  present 
research  with  human  subjects,  the  urine  was  distilled  in  a  large  number  of 
cases  without  the  addition  of  a  hydrolyzing  agent,  while  to  other  portions  of 
the  same  urine  was  added  1  c.  c.  of  concentrated  hydrochloric  acid,  and  they 
were  then  distilled.  In  several  cases,  5  c.  c.  of  85  per  cent  phosphoric  acid 


1  Neubauer:  Arch.  f.  exp.  Path.  u.  Pharm.,  1901,  46,  pp.  135-142. 


STUDIES  OF  URINE  ELIMINATED. 


59 


were  added  to  the  1  c.  c.  of  concentrated  hydrochloric  acid.  The  great 
majority  of  the  determinations  showed  no  difference  in  the  titration  figures 
between  the  distillation  from  the  untreated  urine  and  the  distillation  from 
that  treated  with  the  acid.  There  were,  however,  several  cases  in  which 
the  treatment  with  the  inorganic  acid  gave  a  higher  titration. 

In  the  previous  tables  the  total  alcohol  in  the  urine  as  recorded  was  ob¬ 
tained  by  distillation  with  inorganic  acids,  on  the  basis  that  the  additional 
material  which  was  distilled  was  alcohol.  In  the  experiment  with  subject  A 
on  November  18,  the  free  alcohol  in  the  urine  was  85  mg.,  while  the  conju¬ 
gated  alcohol,  plus  the  free  alcohol,  was  108  mg.  (See  table  8,  p.  39.)  Thus 
there  were  23  mg.  in  the  urine  which  were  in  the  conjugated  state.  With 
subject  D,  March  3,  1916,  the  titration  without  hydrochloric  acid  of  the 
urine  obtained  in  the  second  collection  gave  26  mg.,  and  with  hydrochloric 
acid  gave  37  mg.,  with  a  difference  of  11  mg.  of  conjugated  alcohol.  (See 
table  9,  p.  41.)  With  subject  A,  on  March  27, 1916,  the  free  alcohol  was  99 
mg.,  while  the  total  alcohol  was  129  mg.;  thus  the  conjugated  alcohol  was  30 
mg.  With  subject  C,  on  April  1,  there  were  79  mg.  of  free  alcohol  and  104 
mg.  of  total  alcohol,  or  25  mg.  of  conjugated  alcohol.  (See  table  11,  p.  44.) 

No  efforts  were  made  at  that  time  to  investigate  the  character  of  the  con¬ 
jugation,  but  presumably  it  was  with  glucuronic  acid  as  found  by  Neubauer. 
The  conjugation  of  alcohol  is  of  interest,  as  it  suggests  the  possibility  of  a 
difference  in  the  way  alcohol  may  be  metabolized,  that  is,  it  may  be  coupled 
with  another  substance  and  then  subsequently  oxidized. 

Further  studies  would  be  of  value  in  which  a  glucoside  of  alcohol,  such  as  a 
combination  of  glucose  and  alcohol,  should  be  given  and  the  respiratory  ex¬ 
change  and  the  alcoholic  content  of  urine  studied  to  see  if,  with  this  molecu¬ 
lar  ratio,  there  would  be  a  change  in  the  character  of  the  metabolism  and  in 
the  rate  at  which  alcohol  appeared  in  the  blood  and  urine.  Additional  ex¬ 
periments  might  be  made  to  determine  whether  different  results  would  be 
obtained  with  different  methods  of  introduction,  i.  e.,  by  mouth  or  by  rec¬ 
tum,  in  order  to  ascertain  whether  the  coupling  is  carried  out  through  the 
liver  itself  or  whether  it  is  carried  out  when  the  liver  is  actively  engaged  in 
forming  materials  with  a  possible  secretion  of  a  hormone  distributed  through¬ 
out  the  body.  In  the  latter  case  it  is  not  meant  that  the  transformation 
takes  place  actually  in  the  liver,  but  when  the  liver  is  actively  engaged  in 
metabolic  transformation.  These  suggested  experiments  show  the  great 
value  of  using  ethyl  alcohol  in  rectal  studies  of  humans  from  the  standpoint  of 
pure  physiology. 

EFFECT  OF  RECTAL  INJECTIONS  UPON  VOLUME  OF  URINE 
AND  ELIMINATION  OF  NITROGEN  AND  SODIUM 

CHLORIDE. 

In  addition  to  the  studies  of  the  elimination  and  the  concentration  in  the 
urine  of  alcohol  given  both  by  rectal  injection  and  by  mouth,  observations 
were  made  of  the  volume  of  urine  and  the  nitrogen  and  sodium-chloride  con¬ 
tents  with  rectal  injection.  These  records  were  obtained  not  only  for  the 
experiments  in  which  alcohol  injections  were  given,  but  in  like  experiments 
with  solutions  of  sodium  chloride,  dextrose,  and  levulose.  As  previously 
noted  (p.  23),  the  alcohol  was  diluted  with  distilled  water,  whereas  the 


60 


HUMAN  METABOLISM  WITH  ENEMATA. 


levulose,  and  usually  the  dextrose,  were  given  in  a  0.6  per  cent  solution  of 
sodium  chloride. 

The  results  are  gathered  together  into  tables,  with  records  for  the  individ¬ 
ual  experiments  of  the  dates,  subjects,  volumes  of  solution,  and  weights  of 
the  specific  materials  in  the  solutions.  The  urine  data  are  divided  into  two 
groups.  The  first  group  represents  the  so-called  preliminary  period  and  the 
results  were  obtained  by  analyzing  the  urines  from  the  first  urination,  which 
immediately  preceded  the  experimental  observations.  These  urines  were 
therefore  secreted  during  the  time  between  the  last  urination  previous  to  the 
coming  of  the  subject  to  the  Laboratory  and  that  of  the  first  urination  before 
the  experiment.  It  must  be  borne  in  mind  that  the  length  of  this  prelimi¬ 
nary  period  is  somewhat  uncertain  in  that  the  accuracy  of  the  time  of  the 
previous  urination  depends  wholly  upon  the  subject’s  memory.  Undoubted¬ 
ly  there  is  some  error  in  these  records,  but  as  this  affects  all  the  groups  of  ex¬ 
periments,  the  possible  inaccuracy  is  disregarded,  since  the  chief  object  is  to 
find  whether  there  are  any  characteristic  features  of  the  groups  as  a  whole  in 
respect  to  volume,  nitrogen,  and  sodium  chloride. 

The  second  group  of  data  represents  the  urines  collected  between  the  first 
and  last  urinations  while  the  subject  was  under  observation.  The  length  of 
this  period  of  secretion  is  accurate,  as  the  time  records  were  made  by  the  ob¬ 
server.  The  data  include,  however,  not  only  the  urine  secreted  after  the 
injection  of  the  solution,  but  also  that  secreted  from  the  time  of  the  first 
urination  of  the  subject  at  the  Laboratory  to  the  giving  of  the  injection. 
These  results  therefore  represent  a  mixture  of  the  normal  urine  and  of  urine 
secreted  after  injection,  as  was  the  case  with  the  urines  for  the  long  periods  of 
collection  in  the  discussion  of  elimination  and  concentration  in  the  preceding 
section.  (See  p.  38.)  In  both  groups  records  are  made  of  the  lengths  of 
the  periods  of  secretion,  the  per  hour  values  for  the  volumes  of  urine,  the 
nitrogen  and  the  sodium-chloride  contents,  and  the  ratios  between  these  two 
substances.  The  records  for  the  experimental  urines  also  include  statements 
as  to  the  periods  of  time  after  the  injection  which  are  included  in  the  whole 
periods  of  secretion.  The  ratio  between  the  nitrogen  and  sodium  chloride 
has  no  particular  physiological  significance,  but  is  simply  a  mathematical  ex¬ 
pression  for  determining  the  change  in  the  relationship  after  the  injection  of 
the  solution,  this  indicating  the  difference  between  the  two  factors  in  the 
change  in  rate  of  elimination. 

The  results  obtained  for  injections  of  sodium-chloride  solution  are  first 
discussed,  and  subsequently  those  for  alcohol  injections  in  the  several  con¬ 
centrations,  and  finally  those  for  sugar  solutions. 

Effect  on  Urine  of  Rectal  Introduction  of  a  Solution  of  Sodium 

Chloride. 

In  table  14  the  statistics  are  presented  for  13  experiments  in  which  0.6  per 
cent  solutions  of  sodium  chloride  were  given  and  urines  were  voided  and  col¬ 
lected  both  for  the  preliminary  period  and  for  the  experimental  period  before 
and  after  the  solution  was  injected.  The  volumes  of  the  solution  introduced 
rectally  varied  from  220  c.  c.  to  520  c.  c.,  while  the  sodium  chloride  in  the 
injection  ranged  between  1.3  and  3.1  grams. 

The  length  of  the  preliminary  period  averaged  239  minutes,  with  a  range 
between  120  and  485  minutes,  the  latter  case  being  the  long  experiment  in 


Table  14. — Effect  upon  volume  of  urine  and  elimination  of  nitrogen  and  of  sodium  chloride  of  a  sodium-chloride  solution 

introduced  by  rectum.  ( Values  per  hour.) 


STUDIES  OF  URINE  ELIMINATED. 


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HUMAN  METABOLISM  WITH  ENEMATA. 


1917.  The  volume  of  urine  per  hour  in  the  preliminary  period  was  on  the 
average  60  c.  c.  and  varied  from  25  to  189  c.  c.  The  nitrogen  per  hour 
averaged  465  mg.,  with  a  range  of  221  to  736  mg.  The  average  sodium 
chloride  was  694  mg.,  with  a  variation  from  201  to  1,670  mg.  The  average 
ratio  of  nitrogen  to  sodium  chloride  was  0.88,  with  a  range  from  0.32  to  2.04. 

The  duration  of  the  whole  experimental  period  averaged  311  minutes,  the 
individual  experiments  ranging  in  length  between  205  and  615  minutes. 
This  period  of  secretion  was  therefore  somewhat  longer  than  the  period  be¬ 
fore  the  experiment.  Of  this  311  minutes,  an  average  of  169  minutes  repre¬ 
sented  the  portion  of  time  after  the  injection  of  the  solution  first  began. 
This  part  of  the  period  varied  from  113  to  385  minutes,  except  in  one  experi¬ 
ment,  when  it  was  but  37  minutes.  In  general,  therefore,  over  one-half  of 
the  collection  for  the  experimental  period  represented  urine  which  was  se¬ 
creted  after  the  solution  had  been  given.  The  volume  of  urine  per  hour 
ranged  from  13  c.  c.  to  214  c,  c.,  with  an  average  of  80  c.  c.  This  average  is 
slightly  higher  than  that  for  the  preliminary  period,  but  apparently  this  has 
little  significance  in  showing  that  the  volume  was  greater  in  the  experimental 
period,  for  in  a  number  of  instances  it  was  distinctly  lower  than  that  of  the 
preliminary  secretion.  The  nitrogen  per  hour  averaged  444  mg.,  this  being 
slightly  lower  than  in  the  preliminary  period,  and  ranged  from  302  to  625  mg. 
The  sodium  chloride  was  370  mg.  per  hour,  or  somewhat  more  than  one-half 
that  for  the  preliminary  period,  and  ranged  from  54  to  772  mg.  The  nitro¬ 
gen-sodium  chloride  ratio  was  2.05  on  the  average,  thus  indicating  that, 
relatively,  the  change  in  the  elimination  of  sodium  chloride  was  greater  than 
the  change  in  the  elimination  of  nitrogen. 

The  figures  on  the  whole  are  regular  enough  for  purposes  of  comparison 
with  other  groups.  There  are,  however,  some  extreme  values.  For  exam¬ 
ple,  in  the  nitrogen  data  for  the  preliminary  period,  that  for  the  experiment 
with  A  on  November  21  was  736  mg.,  but  the  corresponding  one  for  the  ex¬ 
perimental  period  was  likewise  high.  The  sodium-chloride  values  in  the 
preliminary  periods  for  C  on  October  21  and  on  November  2  are  distinctly 
high.  The  discussion  of  the  total  effects  of  the  injection  of  the  solution  of 
sodium  chloride  is  reserved  until  all  the  other  material  has  been  presented 
and  will  be  considered  in  connection  with  the  percentile  changes. 

Effect  on  Urine  of  Rectal  Introduction  of  a  5  per  cent 

Solution  of  Alcohol. 

There  were  14  experiments,  in  which  a  5  per  cent  alcohol  solution  was  given 
rectally  and  the  urine  collected  both  before  the  experiment  began  and  during 
the  experiment  itself.  The  data  are  given  in  table  15.  The  volume  of  the 
injection  varied  from  300  c.  c.  to  520  c.  c.,  and  the  amount  of  alcohol  in  these 
quantities  from  15  to  26  grams. 

The  average  length  of  the  period  before  the  experiment  began  was  226 
minutes,  with  variations  from  85  to  700  minutes.  Many  of  the  periods  are 
under  200  minutes,  the  average  being  raised  by  the  long  period  with  B  on 
October  31,  which  really  included  the  urine  for  the  night  preceding  the  ex¬ 
periment.  The  volume  per  hour  averaged  53  c.  c.,  and  varied  from  26  to 
81  c.  c.  The  average  nitrogen  per  hour  was  460  mg.,  with  individual  values 
from  the  low  figure  of  277  mg.  with  B  on  October  31,  to  694  mg.  with  the  same 
subject  on  October  17.  The  sodium  chloride  per  hour  was  574  mg.,  with  a 


Table  15. — Effect  upon  volume  of  urine  and  elimination  of  nitrogen  and  of  sodium  chloride  of  a  5  per  cent  alcohol  solution  introduced 

by  rectum.  ( Values  per  hour.) 


STUDIES  OF  URINE  ELIMINATED. 


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HUMAN  METABOLISM  WITH  ENEMATA. 


variation  of  from  199  mg.  to  1,006  mg.  The  ratio  of  nitrogen  to  sodium 
chloride  was  on  the  average  0.99. 

The  length  of  the  experimental  period  averaged  290  minutes.  This  was 
not  materially  different  from  the  corresponding  average  in  the  sodium-chlo¬ 
ride  experiments,  and  a  like  similarity  may  be  observed  in  the  preliminary 
periods  for  the  two  groups  of  observations.  The  length  of  time  after  the  in¬ 
jection  began  averaged  191  minutes.  The  volume  of  urine  per  hour  was 
130  c.  c.  on  the  average,  somewhat  more  than  double  that  during  the  pre¬ 
liminary  period,  that  is,  a  diuresis.  A  positive  increase  was  found  in  most  of 
the  experiments,  so  that  this  change  represents  an  actual  increase  in  volume 
of  urine  eliminated  after  the  experiment  began.  The  average  nitrogen  per 
hour  was  425  mg.,  a  slightly  lower  figure  than  that  for  the  preliminary  period. 
The  sodium  chloride  per  hour  was  very  decidedly  lower,  i.  e.,  328  mg.  per  hour 
as  compared  with  574  mg.  for  the  preliminary  period.  The  change  in  these 
two  quantities  is  reflected  in  the  average  ratio  of  nitrogen  to  sodium  chloride, 
which  is  1.77  in  the  experimental  period  as  compared  with  0.99  in  the  pre¬ 
liminary  period. 

Effect  on  Urine  of  Rectal  Introduction  of  a  7.5  per  cent  Solution 

of  Alcohol. 

In  10  experiments  a  7.5  per  cent  solution  of  alcohol  was  introduced  rectally 
and  the  urine  collected  before  and  after  the  experiment.  The  data  for  the 
volume  of  urine  and  elimination  of  nitrogen  and  sodium  chloride  are  given 
in  table  16.  Five  of  these  experiments,  made  in  1916,  are  averaged  sep¬ 
arately,  as  they  differed  from  the  rest  of  the  group  in  that  the  experimental 
periods  were  somewhat  shorter  than  in  the  5  experiments  conducted  in  1917. 
In  fact,  the  1917  experiments  were  night  experiments  and  the  length  of  time 
which  the  urine  collection  covered  was  therefore  somewhat  greater. 

In  the  first  group  the  volumes  of  alcohol  solution  injected  ranged  from 
265  to  510  c.  c.,  with  the  amount  of  alcohol  varying  from  19.9  to  37.5  grams. 
The  average  length  of  the  urine  period  preceding  the  experiment  was  179 
minutes.  The  average  volume  of  urine  per  hour  was  50  c.  c.,  the  nitrogen 
per  hour  511  mg.,  the  sodium  chloride  per  hour  580  mg.,  and  the  ratio  of 
nitrogen  to  sodium  chloride  0.93.  For  purposes  of  comparison  these  values 
are  sufficiently  close  in  order  of  magnitude  to  those  obtained  in  the  pre¬ 
liminary  periods  of  the  experiments  with  a  5  per  cent  solution  of  alcohol. 

The  experimental  urine  periods  in  1916  averaged  321  minutes  in  length, 
with  the  portion  of  time  after  the  rectal  injection  246  minutes.  This  is 
slightly  longer  than  the  period  after  injection  with  the  preceding  groups. 
The  volume  of  urine  averaged  135  c.  c.  per  hour  as  compared  with  the  much 
smaller  average  volume  of  50  c.  c.  in  the  preliminary  period.  The  nitrogen 
per  hour  was  442  mg.,  somewhat  lower  than  that  in  the  first  urine  collec¬ 
tion.  The  sodium-chloride  excretion  was  287  mg.  per  hour.  The  ratio  of 
nitrogen  to  sodium  chloride  was  1.75,  showing  a  distinctly  greater  change  in 
the  output  of  sodium  chloride  than  in  the  nitrogen. 

In  the  5  experiments  conducted  in  1917,  all  with  the  same  subject,  37.5 
grams  of  alcohol  were  given  in  500  c.  c.  of  a  7.5  per  cent  solution.  The 
preliminary  period  averaged  160  minutes  in  length,  which  is  comparable 
with  the  average  for  the  first  group.  The  volume  per  hour  was  42  c.  c.,  and 
likewise  comparable  with  the  1916  group.  The  average  nitrogen  per  hour 


Table  16. — Effect  upon  volume  of  urine  and  elimination  of  nitrogen  and  sodium  chloride  of  a  7.5  per  cent  alcohol  solution  introduced 

by  rectum.  ( Values  per  hour.) 


STUDIES  OF  URINE  ELIMINATED 


65 


66 


HUMAN  METABOLISM  WITH  ENEMATA. 


was  531  mg.,  the  sodium  chloride  698  mg.,  and  the  ratio  of  nitrogen  to 
sodium  chloride  0.83.  The  experimental  period  was  much  longer  than  in 
the  1916  group,  namely,  676  minutes  on  the  average,  and  the  time  after  the 
rectal  injection  began  was  478  minutes.  The  volume  per  hour  was  61  c.  c., 
or  slightly  greater  than  in  the  preliminary  period.  The  average  nitrogen 
elimination  per  hour  was  411  mg.,  about  25  per  cent  lower  than  the  nitrogen 
output  in  the  preliminary  period.  The  sodium  chloride  likewise  fell  very 
materially,  averaging  138  mg.  per  hour.  This  change  is  reflected  in  the  much 
higher  ratio  of  nitrogen  to  sodium  chloride  in  the  experimental  period, 
namely,  3.80. 

Effect  on  Urine  of  Rectal  Introduction  of  a  10  per  cent  Solution 

of  Alcohol. 

In  4  experiments  26  to  26.5  grams  of  alcohol  were  given  in  a  10  per  cent 
solution,  that  is,  in  a  volume  of  about  265  c.  c.  (See  table  17.)  The  length  of 
the  preliminary  period  averaged  135  minutes,  the  average  volume  per  hour 
was  64  c.  c.,  while  the  average  nitrogen  elimination  per  hour  was  478  mg. 
and  the  sodium  chloride  per  hour  772  mg.  The  ratio  of  nitrogen  to  sodium 
chloride  was  0.75.  The  quantities  are  therefore  fairly  comparable  with 
those  obtained  in  the  preliminary  periods  of  preceding  groups. 

The  length  of  the  experimental  periods  averaged  301  minutes,  which 
corresponds  generally  with  the  preceding  groups,  except  in  the  case  of  the 
1917  experiments  with  a  7.5  per  cent  solution  of  alcohol.  The  portion  of 
the  period  after  the  rectal  injection  began  was  205  minutes.  The  average 
volume  per  hour  was  133  c.  c.,  twice  that  in  the  preliminary  period.  The 
average  nitrogen  excretion  per  hour  was  374  mg.,  or  a  material  fall  on  the 
average  from  the  excretion  found  in  the  preliminary  period.  The  sodium- 
chloride  output  per  hour  fell  very  considerably,  the  average  being  295  mg. 
This  decrease  was  reflected  in  the  ratio  of  nitrogen  to  sodium  chloride,  which 
was  1.66  as  compared  with  0.75  in  the  preliminary  period. 

Effect  on  Urine  of  Rectal  Introduction  of  a  Dextrose  Solution. 

In  9  experiments  30  grams  of  dextrose  were  introduced  by  rectum  in  500 
to  520  c.  c.  of  a  0.6  per  cent  solution  of  sodium  chloride,  except  on  May  6 
and  16,  when  a  5  per  cent  solution  of  alcohol  was  substituted  for  the  sodium- 
chloride  solution.  The  results  are  given  in  table  18.  The  average  length  of 
the  preliminary  period  before  the  experiment  began  was  266  minutes,  while 
the  average  volume  of  urine  was  68  c.  c.  The  nitrogen  elimination  per  hour 
averaged  502  mg.  and  that  of  sodium  chloride  595  mg.;  the  general  ratio 
between  the  two  was  0.92. 

The  collection  period  for  the  experimental  urine,  i.  e.,  that  secreted  before 
and  after  the  rectal  injection  began,  averaged  363  minutes  in  length,  and  of 
this  the  observations  made  after  the  rectal  injection  commenced  extended 
over  273  minutes.  The  volume  of  urine  was  76  c.  c.  per  hour,  or  a  little  more 
than  that  for  the  preliminary  period.  The  nitrogen  excretion  was  415  mg. 
per  hour,  approximately  20  per  cent  lower  than  that  for  the  preliminary 
period.  The  sodium-chloride  output  was  469  mg.  per  hour,  or  lower  than 
in  the  preliminary  period.  The  ratio  of  nitrogen  to  sodium  chloride  of  1.14 
was  only  slightly  higher  than  the  ratio  for  the  preliminary  period,  thus  indicat¬ 
ing  that  the  changes  in  the  elimination  of  both  the  nitrogen  and  the  sodium 
chloride  were  more  or  less  parallel. 


Table  17. — Effect  upon  volume  of  urine  and  elimination  of  nitrogen  and  sodium  chloride  of  a  10  per  cent  alcohol  solution  introduced 

by  rectum.  ( Values  per  hour.) 


STUDIES  OF  URINE  ELIMINATED. 


67 


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by  rectum.  ( Values  per  hour.) 


68 


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other  experiments  included  in  this  table. 


STUDIES  OF  URINE  ELIMINATED. 


69 


It  should  be  noted  that  although  in  two  of  the  experiments  the  dextrose 
was  injected  in  a  5  per  cent  alcohol  solution  instead  of  in  a  0.6  per  cent  solu¬ 
tion  of  sodium  chloride,  the  results  for  all  the  factors  in  these  two  experiments 
are  not  significantly  different  from  those  in  the  majority  of  the  other 
experiments.  The  sodium-chloride  elimination  and  nitrogen  elimination 
apparently  decreased  about  the  same  degree  in  both  experiments,  as  there 
was  no  large  difference  between  the  ratio  of  nitrogen  to  sodium  chloride 
for  the  preliminary  and  experimental  urines.  Following  the  injection,  the 
volumes  of  urine  were  slightly  higher  in  one  case  than  in  the  preliminary 
period,  and  materially  higher  in  the  other  case,  which  is  somewhat  in  line 
with  the  other  experiments.  Apparently,  in  these  two  experiments,  the 
dextrose  was  more  effective  in  the  regulation  of  the  liquids  in  the  body  than 
was  the  alcohol. 

Two  experiments  are  really  too  few  from  which  to  draw  conclusions,  but 
they  suggest  the  importance  of  carrying  out  experiments  in  which  alcohol  is 
ingested  with  a  sugar  to  find  whether  the  effect  of  alcohol  is  specifically 
different  when  ingested  alone  from  that  when  it  is  ingested  with  sugars. 

Effect  on  Urine  of  Rectal  Introduction  of  a  Solution  of  Levulose. 

In  10  experiments  levulose  was  given  rectally  and  in  a  0.6  per  cent  solution 
of  sodium  chloride.  The  results  are  grouped  in  table  19  according  to  the 
amount  of  levulose  given.  In  the  first  group  of  4  experiments,  25  grams  of 
sugar  were  given  in  a  volume  of  500  c.  c.,  and  in  the  other  6  experiments 
all  but  one  were  made  with  50  grams  of  levulose  and  volumes  of  500  and 
1,000  c.  c. 

With  the  25  grams  of  levulose,  the  length  of  the  preliminary  period  aver¬ 
aged  181  minutes  and  the  volume  of  urine  only  49  c.  c.  per  hour,  which  was 
rather  lower  than  in  most  of  the  preceding  groups.  The  nitrogen  output  per 
hour  was  455  mg.,  while  that  of  the  sodium  chloride  was  610  mg.  The  ratio 
of  nitrogen  to  sodium  chloride  was  0.85. 

The  length  of  the  experimental  period  was  322  minutes.  Of  this,  206 
minutes  were  subsequent  to  the  beginning  of  the  rectal  injection.  The 
volume  of  urine  was  55  c.  c.  per  hour,  only  a  slight  change  from  that  of  the 
preceding  period.  The  nitrogen  output  per  hour  averaged  362  mg.,  a 
decrease  of  93  mg.  per  hour  from  the  nitrogen  found  for  the  preliminary 
period,  while  the  sodium-chloride  excretion  averaged  244  mg.,  or  a  decrease 
of  366  mg.  per  hour  from  the  preliminary  value.  The  ratio  between  the 
nitrogen  and  the  sodium  chloride  was  1.70,  indicating  that  when  the  values 
for  the  preliminary  and  experimental  periods  are  compared  for  these  two 
factors  it  is  found  that  both  excretions  diminished  in  the  experimental  period, 
but  the  decrease  in  the  sodium-chloride  excretion  was  greater  than  the  de¬ 
crease  in  the  nitrogen  excretion. 

With  the  group  of  6  experiments  in  which  the  larger  amount  of  levulose 
was  given,  the  preliminary  period  averaged  159  minutes  and  the  volume  of 
urine  per  hour  70  c.  c.  The  nitrogen  per  hour  was  513  mg.,  while  the  sodium 
chloride  reached  the  very  high  average  value  of  1,125  mg.  In  3  of  the 
experiments  the  sodium-chloride  elimination  was  over  1  gram  per  hour. 
This  large  elimination  consequently  lowered  the  ratio  between  nitrogen  and 
sodium  chloride  to  0.54. 

The  length  of  the  experimental  period  was  291  minutes,  the  part  following 


Table  19. — Effect  upon  volume  of  urine  and  elimination  of  nitrogen  and  sodium  chloride  of  levulose  solution  introduced  by  rectum.  ( Values  per  hour.) 


70 


HUMAN  METABOLISM  WITH  ENEMATA 


Experimental  urine 
(before  and  after  levulose  given). 

Ratio 

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NaCl 

CO  rH  rf  lO 
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N  H  H 

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NCONN^h 

291 

Preliminary  urine 
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Ratio 

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NaCl 

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rH 

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CKNiOOCDH 

00  N  iO  <D  H  iO 

.54 

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610 

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g  H  N  H  rl 

181 

O  lO  IO  IO  lO  IO 

O  <M  rH  CO  CO 

d  Cl  H  rl  H  H 

159 

Solution 

injected. 

Weight 

of 

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STUDIES  OF  URINE  ELIMINATED. 


71 


the  levulose  injection  being  177  minutes;  both  of  these  were  slightly  lower 
than  in  most  of  the  preceding  groups.  The  volume  of  urine  per  hour 
averaged  74  c.  c.  as  compared  with  70  c.  c.  in  the  preliminary  period,  while 
the  nitrogen  excretion  per  hour  was  very  materially  lower — 321  mg.  as 
compared  with  513  mg.  The  sodium  chloride  per  hour  likewise  decreased, 
with  an  average  of  but  306  mg.  The  ratio  of  nitrogen  to  sodium  chloride  of 
1.17  showed  no  characteristic  change. 

The  findings  in  the  values  for  the  nitrogen  elimination  after  the  injection 
of  levulose  are  of  interest  because  of  the  materially  decreased  elimination. 
They  would  point  to  the  possibility  of  levulose  acting  as  a  sparer  of  protein. 
The  indications  are,  however,  that  levulose  is  not  actually  metabolized  im¬ 
mediately  when  injected  by  rectum.  Consequently,  it  is  a  problem  as  to  what 
the  mechanism  is  by  which  the  rectal  injection  of  levulose  can  result  in  a 
sparing  action  upon  protein  metabolism. 

Summary  of  results  on  urines  of  preliminary  periods. — While  the  prelimi¬ 
nary  periods  in  the  second  group  of  levulose  experiments  present  an  excep¬ 
tional  value  for  the  ratio  between  nitrogen  and  sodium  chloride,  it  has  been 
frequently  shown  in  the  preceding  discussion  that  the  values  of  one  group  of 
preliminary  periods  were  comparable  with  values  in  the  preceding  or  follow¬ 
ing  groups.  It  was  not  originally  intended  in  collecting  these  urines  in  the 
preliminary  periods  to  secure  values  for  normal  urine  excretions,  but  mainly 
to  obtain  a  basis  for  estimating  the  effect  of  the  rectal  injection  of  the  differ¬ 
ent  substances  upon  the  volume,  nitrogen,  and  sodium  chloride.  If,  however, 
the  averages  of  the  values  in  the  preliminary  periods  were  markedly  different 
in  one  group  than  in  another,  it  would  be  questionable  whether  one  could 
compare,  for  example,  the  rectal  injection  of  a  sodium-chloride  solution  with 
the  effect  of  rectal  injection  of  alcohol  or  sugar  solutions.  An  examination  of 
the  several  tables  shows  that  there  are  marked  individual  variations  in  any 
single  group  by  itself.  These  may  be  due  to  inaccuracies  on  the  part  of  the 
subjects  who  reported  the  times  of  previous  urinations;  they  may  be  due  to 
the  effect  of  the  preceding  diet,  which  varied  in  character;  or  they  may  be 
caused  by  variations  in  the  water  balance  and  equilibrium  in  the  body,  which 
might  be  variously  affected  by  the  rectal  injection  according  to  whether  the 
body  was  in  a  partially  dehydrated  condition  or  supplied  with  a  surplus  of 
water. 

The  number  of  experiments  in  the  several  groups  varied  from  4  to  14  and 
the  length  of  the  preliminary  periods  varied  on  the  average  from  135  to  266 
minutes.  The  value  of  266  minutes  is  found  in  the  dextrose  series  and  is 
high  because  of  the  inclusion  of  the  experiment  on  February  22  in  which  the 
length  of  the  preliminary  period  was  780  minutes.  If  this  figure  is  excluded, 
the  average  for  the  dextrose  experiments  is  202  minutes  which  is  close  to  the 
general  average  (193)  of  the  various  groups.  It  will  thus  be  seen  that  the 
preliminary  urines  covered  in  general  a  range  of  time  which  is  fairly  com¬ 
parable  from  one  group  to  another.  The  average  volume  for  the  8  groups 
was  57  c.c.  per  hour,  while  the  range  is  from  42  c.c.  in  the  second  group  of  ex¬ 
periments  in  which  7.5  per  cent  alcohol  was  injected  to  70  c.c.  in  the  second 
group  with  the  rectal  injection  of  levulose.  The  range  is  not  wide  consider¬ 
ing  that  the  groups  varied  in  the  number  of  experiments  and  that  the  experi¬ 
ments  in  the  different  groups  are  not  proportionately  well  divided  among  the 
3  or  4  subjects.  The  average  nitrogen  elimination  of  all  the  groups  is  489 


72 


HUMAN  METABOLISM  WITH  ENEMATA. 


mg.  per  hour,  while  the  range  is  from  455  to  531  mg.  per  hour.  The  varia¬ 
tions  from  the  average  are  uniform,  that  is  to  say,  4  of  the  group  are  above 
the  average  and  4  are  below.  The  average  sodium  chloride  per  hour  of  all 
the  groups  was  706  mg.  The  range  was  574  to  1,125  mg.  per  hour.  The 
latter  value  is  in  the  second  group  of  levulose  experiments  in  which  the 
sodium-chloride  elimination  in  the  preliminary  period  is  distinctly  high  in  3 
of  the  6  experiments. 

The  ratio  of  nitrogen  to  sodium  chloride  is  on  the  average  in  the  8  groups 
0.84,  the  range  being  from  0.54  to  0.99.  The  lower  value  is  found  with  the 
second  group  of  levulose  experiments  and  is  due  to  the  very  high  elimination 
of  sodium  chloride  in  this  group.  Excluding  this  value  the  range  is  from  0.75 
to  0.99,  a  rather  narrow  range  considering  that  this  is  a  ratio  between  two 
entirely  different  substances,  one  of  which  comes  from  a  material  which  enters 
into  the  metabolism,  namely  protein,  and  the  other  (sodium  chloride)  has 
much  to  do  with  the  equilibrium  of  fluids.  It  would  seem  as  though  this 
ratio  would  be  of  value  in  indicating,  in  any  data  which  are  gathered,  as  to 
whether  there  is  an  abnormal  condition  of  the  diet  and  metabolism  with 
regard  to  either  nitrogen  or  sodium  chloride. 

This  examination  of  the  preliminary  averages  and  ranges  shows  that  in 
general  these  groups  are  sufficiently  similar  to  be  termed  comparable  and  that 
therefore  the  data  were  obtained  from  urines  which  were  secreted  under,  on 
the  average,  similar  conditions.  This  fact  is  of  importance  because  signifi¬ 
cance  can  then  be  attached  to  any  material  changes  which  occur  in  the  group 
figures  for  the  experimental  urines  as  the  result  of  the  injection  of  the  various 
solutions.  Changes  have  more  significance  when  it  is  recalled  that  a  portion 
of  the  experimental  period  includes  urine  which  was  secreted  before  the 
injection  began. 

Percentile  Changes  in  Urinary  Volume,  and  in  Elimination  of 
Nitrogen,  and  of  Sodium  Chloride  as  Affected 
by  Rectal  Injection. 

In  order  to  bring  out  more  clearly  the  relative  as  well  as  the  absolute 
changes  in  elimination  of  sodium  chloride  and  nitrogen,  and  the  changes  in 
volume  of  urine  after  rectal  injection  of  various  substances,  a  summary  table 
of  the  percentile  increases  or  decreases  in  these  quantities  has  been  made. 
(See  table  20.)  This  records  the  kind  of  material  injected,  the  volume  of 
the  injection,  the  weight  of  the  substance  in  the  injection,  the  number  of 
experiments  included  in  the  summary  for  each  substance,  the  average  length 
of  the  preliminary  period,  and  finally  the  average  length  of  the  second  or 
experimental  period,  which  included  the  time  after  the  rectal  injection. 
The  percentage  of  this  latter  period  which  was  occupied  by  the  time  after 
injection  is  likewise  given. 

The  last  8  columns  of  the  table  record  the  percentile  changes  in  the 
elimination  for  the  three  quantities — volume,  nitrogen,  and  sodium  chloride, 
and  also  the  percentile  changes  in  the  nitrogen  to  sodium  chloride  ratio. 
Under  each  of  these  four  heads  the  average  change  is  expressed  in  two  ways: 
(1)  a  simple  arithmetical  average  or  mean,  calculated  without  regard  to 
sign;  and  (2)  an  algebraical  average  in  which  the  plus  and  minus  signs  are 
taken  into  consideration  in  totaling  and  averaging  the  individual  values. 
The  first  indicates  the  general  amount  of  variation,  and  the  second  the 


Table  20. — Summary  table  of  percentile  changes  in  volume  of  urine,  and  elimination  of  nitrogen  and  sodium  chloride  after  rectal  injection  of  various 

substances  in  solution. 


STUDIES  OF  URINE  ELIMINATED 


73 


Percentile  changes  in  elimination  for  experimental  period. 

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74 


HUMAN  METABOLISM  WITH  ENEMATA. 


general  direction  of  the  variation.  The  average  without  regard  to  sign  is  of 
importance  in  that  it  indicates  the  degree  of  significance  to  be  attached  to 
the  directional  effect  as  shown  by  the  average  with  regard  to  sign.  That  is 
to  say,  when  the  directional  effect  is  accompanied  by  a  considerably  larger 
average  without  regard  to  sign,  thus  showing  a  large  amount  of  fluctuation 
in  plus  and  minus  values,  the  average  with  regard  to  sign  has  less  significance 
than  would  be  the  case  if  the  two  averages  were  more  nearly  alike. 

From  table  20  we  find  that  the  number  of  experiments  in  the  several 
groups  differed  somewhat,  ranging  from  4  to  14  experiments.  While  the 
average  lengths  of  the  preliminary  periods  varied  from  135  minutes  to  266 
minutes,  their  durations  are,  in  general,  sufficiently  uniform  for  purposes  of 
comparison.  Omitting  the  676  minutes  of  the  all-night  experiments  with 
7.5  per  cent  alcohol  solution,  we  find  that  the  lengths  of  the  experimental 
periods  varied  from  290  minutes  to  363  minutes.  The  proportion  of  the 
total  experimental  period  which  is  represented  by  the  period  after  the  in¬ 
jection  began  ranged  on  the  average  from  52  to  76  per  cent,  which  is  in 
general  somewhat  narrow. 

PERCENTILE  CHANGES  IN  VOLUME  OF  URINE. 

The  percentile  changes  in  the  volume  of  urine  may  first  be  considered.  It 
must  be  recognized  that,  other  things  being  equal,  if  a  quantity  of  liquid  is 
injected  into  the  body,  there  will  follow,  some  time  or  other,  the  elimination 
of  this  quantity  of  liquid  or  similar  quantities  in  order  to  maintain  an  equi¬ 
librium  of  fluid.  The  quantity  of  solution  injected  in  these  experiments 
varied  from  220  c.  c.  to  1,000  c.  c.  It  must  also  be  recalled  that  in  the  sodium 
chloride,  dextrose,  and  levulose  experiments,  the  solution  contained  the 
equivalent  of  0.6  per  cent  sodium  chloride,  while  this  was  absent  from  the 
alcohol  solution.  One  would  therefore  anticipate  a  difference  in  the  charac¬ 
ter  of  the  urine  eliminated  according  to  whether  or  not  the  original  solution 
contained  sodium  chloride. 

In  the  experiments  with  a  sodium-chloride  solution,  there  was,  on  the 
average,  a  change  in  volume  of  ±70  per  cent.  When  the  plus  and  minus 
signs  are  taken  into  consideration  in  calculating  the  average,  a  directional 
effect  of  +52  per  cent  is  obtained,  i.  e.,  a  positive  increase  in  volume.  This 
change  is  confirmed  by  the  fact  that  in  only  4  of  the  13  experiments  was 
there  an  actual  decrease  in  volume. 

The  change  in  the  elimination  of  urine  after  the  injection  of  300  to  520  c.  c. 
of  a  5  per  cent  alcohol  solution  was,  on  the  average,  ±  161  per  cent.  This 
is  practically  an  increase,  as,  taking  into  account  the  small  decrease  in  the 
experiment  with  B  on  October  17,  and  that  with  C  on  November  8,  we  find 
the  algebraic  average  to  be  +157  per  cent. 

With  a  7.5  per  cent  alcohol  solution,  all  of  the  experiments  in  the  first  group 
indicated  an  increase  in  the  volume  of  urine  and  thus  both  the  arithmetical 
and  the  algebraic  averages  show  a  positive  change  of  + 193  per  cent.  The  en¬ 
tire  group  of  night  experiments  in  which  the  7.5  per  cent  alcohol  solution  was 
given  likewise  gave  increased  volumes  of  urine  in  the  experimental  periods, 
but  on  a  lower  level  than  the  shorter  experiments,  the  average  increase  being 
but  +47  per  cent.  We  may  conclude,  therefore,  that  if  the  urine  is  measured 
for  a  short  time  after  a  7.5  per  cent  alcohol  solution  is  injected,  there  is  a  very 
marked  increase  in  the  volume  of  urine  eliminated,  but  if  the  time  is  extended 


STUDIES  OF  URINE  ELIMINATED. 


75 


somewhat  before  the  urine  is  finally  voided,  the  increase  is  not  so  great. 
It  would  thus  appear  that  this  effect  of  the  alcohol  continues  not  more  than 
3  or  4  hours. 

With  the  injection  of  265  c.  c.  of  a  10  per  cent  alcohol  solution  in  4 
experiments,  there  was  an  average  change  of  141  per  cent  in  the  volume 
of  urine  eliminated.  This  was  a  positive  increase  in  volume  in  all  four 
cases. 

When  30  grams  of  dextrose  were  injected  in  500  to  520  c.  c.  of  a  0.6  per  cent 
solution  of  sodium  chloride,  the  average  change  without  regard  to  sign  was 
±  109  per  cent.  Taking  into  consideration  the  plus  and  minus  signs,  how¬ 
ever,  we  find  that  there  was  an  average  increase  in  volume  in  the  experimen¬ 
tal  period  of  73  per  cent,  that  is,  there  was  a  greater  elimination  of  urine  with 
a  rectal  injection  of  the  dextrose  solution  than  there  was  without  it.  On  the 
other  hand,  of  the  9  dextrose  experiments,  there  were  3  in  which  the  volume 
of  urine  was  less  than  in  the  preliminary  period.  Furthermore,  in  two  of  the 
remaining  6  experiments,  the  dextrose  was  combined  with  a  5  per  cent  alcohol 
solution;  consequently,  in  these  two  experiments  (with  A  on  May  6  and  May 
16)  the  effect  of  the  alcohol  upon  the  volume  of  urine  eliminated  shown  in  the 
preceding  groups  of  experiments  must  be  taken  into  consideration.  While 
the  algebraic  average  for  the  entire  group  is  +73  per  cent,  rather  than  ±  109 
per  cent,  it  would  hardly  be  wise  to  draw  a  general  conclusion  that  there  was 
actually  an  average  positive  increase  in  the  volume  of  urine  eliminated  as  a 
result  of  the  rectal  injection  of  the  dextrose  solution. 

The  levulose  experiments  are  averaged  in  two  groups,  those  with  25  grams 
of  levulose  in  a  500  c.  c.  solution  and  those  with  50  grams  (including  one,  also, 
with  37.5  grams)  in  a  500  to  1,000  c.  c.  solution.  In  the  first  group,  there  was 
a  change  in  volume  of  ±34  per  cent,  but  when  the  direction  of  the  change  is 
regarded,  it  is  found  that  actually  there  was  a  change  of  only  +7  per  cent  in 
the  volume.  The  individual  experiments  are  equally  divided  as  to  the  char¬ 
acter  of  the  effect;  consequently  it  is  doubtful  if  with  this  amount  of  levulose 
the  change  in  the  volume  is  positive  one  way  or  the  other,  and  the  direction  of 
the  change  may  depend  entirely  upon  the  conditions  of  the  experiment. 

With  the  larger  amounts  of  levulose  there  was  an  average  change  in  volume 
of  urine  of  ±46  per  cent  or,  when  the  direction  of  the  effect  is  noted,  of  +15 
per  cent.  But  here  again,  since  in  3  of  the  experiments  a  decrease  in  volume 
was  found,  in  2  an  increase,  with  no  change  in  the  sixth  experiment,  it  is  clear 
that  there  was  no  positive  change  in  one  direction  or  the  other  during  the 
experimental  period. 

The  general  conclusion  may  be  drawn  from  these  findings  in  respect  to 
changes  in  volume  of  urine  as  a  result  of  rectal  injection  of  various  substances 
that  the  alcohol  solution  produced  the  most  positive  increase  in  the  volume 
of  urine  when  it  was  given  by  this  method.  The  0.6  per  cent  solution  of 
sodium  chloride  ranks  next  with  a  positive  change  in  the  majority  of  in¬ 
stances,  and  dextrose  produced  a  positive  change  in  many  instances.  Levu¬ 
lose  was,  on  the  whole,  neither  negative  nor  positive  with  respect  to  change 
in  volume  with  rectal  injection. 

It  may  be  concluded,  therefore,  that  alcohol  in  concentrations  varying 
from  5  to  10  per  cent,  when  injected  rectally,  acts  as  a  diuretic  and  increases 
the  volumes  of  urine  eliminated.  As  alcohol  is  metabolized,  this  increase  is 
apparently  a  specific  effect  of  the  alcohol  itself  and  not  an  accompaniment  of 


76 


HUMAN  METABOLISM  WITH  ENEMATA. 


metabolism.  Neither  is  it  an  increase  in  volume  for  the  purpose  of  eliminat¬ 
ing  foreign  substances,  such  as  /3-oxybutyric  acid  in  diabetes. 

One  would  expect  that  the  injection  of  a  0.6  per  cent  sodium-chloride  solu¬ 
tion  would  not  change  the  volume  of  urine  eliminated,  as  this  would  be  the 
introduction  into  the  body  of  a  fluid  which  was  already  present  in  equilibrium 
with  the  body-fluids.  An  increase  in  the  volume  of  urine  eliminated  would 
therefore  be  an  indication  that  a  superfluous  amount  of  liquid  had  been  sup¬ 
plied  to  the  body,  and  accordingly  water  had  to  be  eliminated.  This  subject 
is  of  interest  in  connection  with  the  relieving  of  thirst  by  rectal  injection,  this 
method  or  intravenous  introduction  being  usual  when  fluids  can  not  be  in¬ 
troduced  by  mouth. 

As  will  be  seen  later,  there  is  an  indication  that  the  dextrose  introduced 
rectally  is  actually  metabolized.  Consequently,  the  fluid  in  the  solution 
need  not  be  retained,  for  when  the  dextrose  is  used,  the  water  in  the  solution 
would  be  more  than  is  needed  for  maintaining  the  equilibrium  and  conse¬ 
quently  it  would  be  excreted.  The  results  obtained  with  dextrose  give 
somewhat  unusual  significance  to  the  small  change  in  volume  of  urine  which 
is  found  when  levulose  solutions  are  introduced.  In  5  out  of  10  of  the  levu- 
lose  experiments,  the  volume  excreted  after  the  injection  was  less  than  the 
volume  excreted  before  the  injection,  showing  a  retention  of  fluid  when  levu¬ 
lose  was  introduced.  Whether  this  indicates  that  the  liquid  was  retained 
because  the  levulose  was  not  used,  or  whether  such  retention  is  an  accom¬ 
paniment  of  metabolism — which  are  as  yet  but  hypotheses — cannot  be  as¬ 
certained  from  these  experiments  alone. 

Simultaneous  determinations  of  the  levulose  in  the  blood,  the  absorption 
from  the  rectum,  the  volume  of  urine,  and  the  freezing-point  of  urine  and 
blood,  and  also  a  determination  of  the  respiratory  exchange,  would  be  needed 
in  order  even  to  approximate  a  solution  of  this  problem.  It  is  evident  that 
levulose,  when  introduced  rectally,  behaves  differently  from  dextrose  so  far 
as  the  matter  of  liquid  equilibrium  in  the  body  is  concerned,  and  one  must 
infer  that  there  is  a  difference  in  the  character  of  the  metabolism  between  the 
two  sugars  with  this  method  of  introduction. 

PERCENTILE  CHANGES  IN  NITROGEN  ELIMINATION. 

The  average  changes  in  the  nitrogen  elimination  with  the  injection  of  a 
sodium-chloride  solution  is  ±25  per  cent,  but  expressed  algebraically  it  is 
only  +2  per  cent.  Of  the  13  experiments,  4  showed  an  increase  of  nitrogen 
with  the  injection,  and  the  changes  are  sufficiently  large  to  affect  the  average 
for  the  other  9  experiments  in  which  the  nitrogen  decreased.  Consequently, 
a  rectal  injection  of  sodium  chloride  has,  on  the  average,  no  positive  effect  in 
increasing  or  decreasing  the  nitrogen  elimination  in  these  experiments. 

When  a  5  per  cent  solution  of  alcohol  was  injected,  there  was  an  average  for 
14  experiments  of  ±17  per  cent  in  the  nitrogen  elimination,  or  —5  per  cent 
when  the  varying  signs  are  taken  into  consideration.  The  latter  average, 
though  small,  really  indicates  a  definite  lowering  in  the  nitrogen  elimination, 
inasmuch  as  but  3  experiments  out  of  the  14  experiments  gave  an  increase  in 
nitrogen  elimination. 

When  a  7.5  per  cent  solution  of  alcohol  was  injected,  the  average  change  in 
nitrogen  elimination  for  the  group  of  shorter  experiments  was  ±17  per  cent, 
while  the  average  for  the  group  of  longer  experiments  was  ±25  per  cent. 


STUDIES  OF  URINE  ELIMINATED. 


77 


Correcting  these  two  averages  for  the  variation  in  signs,  we  have  —  9  per  cent 
for  the  short  experiments  and  — 19  per  cent  for  the  night  observations.  As 
in  the  first  group  there  were  only  two  small  increases  in  the  individual  experi¬ 
ments  and  in  the  second  group  but  one  small  increase,  evidently  the  nitrogen 
elimination  decreased  with  the  injection  of  a  7.5  per  cent  solution  of  alcohol, 
that  is,  for  a  period  within  3  to  8  hours  after  the  beginning  of  the  injection. 

For  4  experiments  in  which  a  10  per  cent  alcohol  solution  was  used,  with 
26.5  grams  of  alcohol,  there  was  a  change  of  ±26  per  cent  in  the  nitrogen 
elimination.  In  only  one  of  the  4  experiments  was  there  an  increase  in  the 
nitrogen  output  (21  per  cent).  This  group  of  experiments  thus  showed  an 
actual  decrease  of  at  least  16  per  cent  in  the  average  amount  of  nitrogen 
eliminated  within  the  3  hours  following  the  injection. 

In  the  9  experiments  with  injection  of  dextrose  the  average  change  was 
±25  per  cent.  Correcting  for  the  2  experiments  in  which  there  was  an  in¬ 
creased  elimination  gives  an  average  of  — 13  per  cent.  The  other  7  experi¬ 
ments  had  a  decrease  in  the  nitrogen  elimination  varying  from  —  9  to  —  35 
per  cent,  that  is,  on  the  whole  there  was  a  fall  in  the  nitrogen  elimination. 

In  the  first  group  of  experiments  with  an  injection  of  levulose  solution, 
there  was  a  change  of  —21  per  cent  which  is  representative  of  the  whole 
group,  as  in  no  one  of  the  four  experiments  was  there  an  increase  in  the  nitro¬ 
gen  elimination  in  the  urine.  In  the  second  group  of  6  experiments,  there  was 
but  1  experiment  with  an  increase  in  nitrogen  elimination  (+28  per  cent). 
The  general  average  for  the  second  group  was  ±  38  per  cent,  with  a  net  change 
of  —28  per  cent.  This  average  is  larger  than  that  for  any  of  the  other 
groups. 

Considering  the  nitrogen  elimination  for  the  whole  series  of  experiments, 
we  find  that  the  injection  of  the  sodium-chloride  solution  changed  it  the 
least,  while  the  use  of  a  5  per  cent  alcohol  solution  produced  but  little  more 
variation.  With  the  other  three  groups  of  alcohol  experiments  there  was  a 
more  or  less  definite  decrease  in  the  amount  of  nitrogen  eliminated.  With 
dextrose  the  average  decrease  was  not  so  large,  but  still  fairly  positive  in  that 
there  was  a  lower  elimination  of  nitrogen  after  the  taking  of  the  solution. 
With  the  levulose,  however,  the  changes  were  decisive  and  probably  more 
marked  than  with  any  of  the  other  groups,  for  there  was  a  definite  decrease  in 
the  nitrogen  elimination  in  both  groups  of  experiments,  with  but  1  experi¬ 
ment  out  of  10  in  which  there  was  an  increase.  With  the  definite  increase  in 
the  volume  of  urine  eliminated  after  the  injection  of  alcohol  solutions,  one 
would  expect  likewise  an  increased  elimination  of  nitrogen,  that  is,  a  washing- 
out  effect.  On  the  contrary,  however,  there  is  actually  less  nitrogen  elimi¬ 
nated  in  the  experimental  period  after  rectal  injection  of  alcohol  than  before, 
so  that  the  increased  volume  of  urine  does  not  result  in  an  increased  nitrogen 
elimination.  The  increased  volume  must,  therefore,  be  due  to  the  specific 
effect  of  alcohol  upon  the  water  balance  itself.  It  is  of  interest  that  the  in¬ 
gestion  of  a  substance  like  alcohol  can  actually  bring  about  an  increased 
water  elimination  without  affecting  the  amount  of  nitrogen  and  sodium 
chloride  eliminated.  With  levulose  we  have  on  the  other  hand  a  decreased 
nitrogen  elimination  without  a  simultaneous  decreased  water  elimination, 
and  it  would  seem  as  though  this  decrease  was  actually  due  to  the  sparing 
effect  of  levulose  upon  the  protein  metabolism. 

The  fact  that  with  levulose  the  elimination  of  nitrogen  likewise  decreased 


78 


HUMAN  METABOLISM  WITH  ENEMATA. 


is  rather  striking.  This  decrease  cannot  be  due  to  a  smaller  elimination  of 
urine,  that  is,  an  actual  retention  of  liquid,  as  the  amount  of  urine  eliminated 
in  the  experimental  period  increased,  on  the  average,  over  the  amount 
eliminated  in  the  preliminary  period  (  +  7  and  +15  per  cent).  It  would 
seem  as  though  the  levulose  introduced  rectally  acted  as  a  protective  mate¬ 
rial  in  the  metabolism  of  protein.  In  view  of  the  fact  that  the  respiratory 
exchange  of  these  subjects  (see  p.  155  )  does  not  indicate  any  considerable 
utilization  of  levulose  in  the  metabolism,  this  is  rather  puzzling.  One  might 
conclude  that  the  levulose  was  deposited  as  glycogen  or  was  substituted  for 
the  carbohydrate  already  being  utilized.  However,  one  would  not  expect 
that  glycogen  deposit  or  substitution  for  carbohydrate  would  result  in  a 
decrease  in  the  elimination  of  nitrogen.  At  present  such  decrease  can  not 
be  explained.  Further  consideration  of  the  protein-sparing  effect  of  these 
materials  will  be  given  in  the  final  discussion  of  the  results.  (See  p.  159.) 

PERCENTILE  CHANGES  IN  ELIMINATION  OF  SODIUM  CHLORIDE. 

In  the  experiments  in  which  sodium  chloride  was  injected,  its  elimination 
in  the  experimental  period  changed  on  the  average  ±62  per  cent.  When 
corrected  for  the  variation  in  signs,  this  average  was  —32  per  cent  for  the 
whole  group,  with  but  two  experiments  in  which  the  sodium-chloride  elimina¬ 
tion  actually  increased  over  that  in  the  preliminary  period.  This  occurred 
in  spite  of  the  fact  that  the  sodium  chloride  injected  in  the  experimental 
period  varied  from  1.3  to  3.1  grams,  that  it  was  given  in  an  isotonic  solution, 
and  that  the  greater  volume  of  urine  might  be  expected  to  carry  off  the  sur¬ 
plus  sodium  chloride.  Apparently,  however,  the  salt  was  retained  in  the 
body,  or,  at  least,  the  effect  of  the  preceding  diet  was  so  great  upon  the 
elimination  of  the  preliminary  period  as  to  cause  a  much  larger  output 
of  sodium  chloride  than  during  the  experimental  period,  notwithstanding  the 
fact  that  in  the  later  period  sodium  chloride  was  added  to  the  liquids  of 
the  body. 

When  a  5  per  cent  solution  of  alcohol  was  injected  in  14  experiments,  there 
was  a  change  in  the  sodium-chloride  excretion  of  ±  65  per  cent.  When  this 
average  is  corrected  for  the  increase  in  3  experiments,  the  true  average 
change  for  the  whole  group  is  found  to  be  —  25  per  cent-  Consequently,  in 
this  series  also  there  is  clearly  a  reduction  in  the  amount  of  sodium  chloride 
eliminated.  Here,  however,  we  must  recall  the  fact  that  the  solution  injected 
contained  no  sodium  chloride  and  that  the  decrease  may  be  a  natural  one  re¬ 
sulting  from  the  diminishing  effect  of  the  preceding  diet.  With  a  7.5  per  cent 
alcohol  solution  there  was  a  consistent  lowering  in  the  amount  of  sodium  chlo¬ 
ride  eliminated  in  both  groups,  so  a  consideration  of  the  direction  of  the  change 
does  not  affect  the  average  result.  For  the  first  group  it  was  —49  per  cent 
and  for  the  other  —81  per  cent.  These  large  changes  may  be  due  not  only 
to  an  actual  decrease  in  elimination  as  a  result  of  a  depleted  store,  but  also 
to  an  attempt  to  conserve  the  sodium  chloride  present  in  the  body. 

With  the  10  per  cent  solution  of  alcohol  a  like  picture  is  shown,  namely,  a 
consistent  decrease  in  elimination,  with  an  average  change  of  —46  per  cent. 

With  the  dextrose  usually  given  in  a  sodium-chloride  solution,  there  was 
an  average  excretion  of  sodium  chloride  of  ±54  per  cent.  In  3  of  the  9 
experiments,  the  output  of  sodium  chloride  increased  in  the  experimental 
period,  so  that  the  average  when  calculated  algebraically  was  lowered  to  —  9 


STUDIES  OF  URINE  ELIMINATED. 


79 


per  cent.  It  would  appear,  therefore,  that  in  the  majority  of  cases  the 
elimination  of  sodium  chloride  decreased,  but  this  decrease  does  not  seem  so 
definite  or  regular  as  with  the  preceding  alcohol  groups. 

When  levulose  was  given  in  a  sodium-chloride  solution,  the  elimination  of 
sodium  chloride  averaged  —58  per  cent  in  one  group  and  —67  per  cent  in 
the  other.  The  picture  was  entirely  consistent  throughout  each  group. 

PERCENTILE  CHANGES  IN  RATIO  OF  NITROGEN  TO  SODIUM  CHLORIDE. 

The  nitrogen  to  sodium-chloride  ratio,  as  explained  in  the  introduction  to 
this  section,  has  probably  no  profound  physiological  significance,  but  is 
simply  a  mathematical  expression  of  the  change  in  elimination  of  nitrogen 
and  sodium  chloride  in  their  relationship  to  one  another.  Taking  the  ex¬ 
periments  as  a  whole,  we  find  that  the  smallest  change  in  this  ratio  was  with 
dextrose,  on  the  bases  of  both  amount  and  direction,  the  actual  average  with  . 
regard  to  sign  being  +25  per  cent.  Interpreting  this  from  the  point  of  view 
stated  above,  we  may  say  that  with  the  dextrose  solution  the  rates  of  change 
in  the  eliminations  of  nitrogen  and  of  sodium  chloride  were  fairly  the  same. 
As  a  matter  of  fact,  in  this  case  the  change  was  slightly  greater  with  the 
nitrogen  elimination,  although  in  the  series  with  the  other  substances  the 
reverse  was  true. 

The  greatest  change  in  the  ratio  was  with  500  c.  c.  of  a  7.5  per  cent  alcohol 
solution,  the  average  being  +362  per  cent,  due  mathematically  to  the  greater 
decrease  in  the  elimination  of  sodium  chloride.  In  considering  this  ratio 
it  must  be  remembered  that  in  these  experiments  the  urine  after  injection 
was  collected  subsequent  to  an  all-night  period,  with  an  average  length  of 
676  minutes,  and  that  the  results  were  compared  with  those  obtained  in  a 
fairly  short  preliminary  period,  averaging  but  160  minutes. 

SUMMARY  OF  PERCENTILE  CHANGES  WITH  RECTAL  INJECTION. 

The  most  prominent  features  in  the  percentile  changes  of  the  volume  of 
urine  are  (1)  the  decided  increase  in  volume  when  a  solution  of  alcohol  was 
given  alone,  which  was  practically  without  exception;  and  (2)  the  smallest 
increase  in  volume  when  levulose  was  given  in  a  0.6  per  cent  solution  of 
sodium  chloride  (+7  and  +15  per  cent).  The  second  statement  has  the 
more  interest  if  it  be  noted  that  when  another  carbohydrate  was  used  (dex¬ 
trose)  in  a  0.6  per  cent  solution  of  sodium  chloride,  there  was  an  average 
increase  in  volume  of  79  per  cent,1  whereas  when  the  same  solution  was  given 
without  dextrose,  the  volume  increased  on  the  average  52  per  cent.  When 
levulose  was  added  to  the  sodium-chloride  solution,  therefore,  the  change  in 
volume  was  least,  whereas  when  another  carbohydrate  (dextrose)  was  com¬ 
bined  with  the  sodium  chloride,  the  volume  of  urine  did  not  decrease,  but, 
if  anything,  it  was  increased. 

With  the  nitrogen  elimination  the  two  striking  points  are  the  very  small 
average  increase  when  a  sodium-chloride  solution  was  given  alone  and  a 
uniformly  average  decrease  in  the  nitrogen  elimination  with  the  other  groups 
of  experiments,  particularly  when  levulose  was  given  in  a  sodium-chloride 
solution.  The  changes  with  dextrose  and  with  alcohol  solutions  were  in  the 
same  direction  as  those  for  levulose,  but  were  not  so  large. 


1In  calculating  the  percentage  for  this  comparison,  the  two  experiments  in  which  an  alcohol 
solution  was  used  (May  6  and  16)  were  omitted. 


80 


HUMAN  METABOLISM  WITH  ENEMATA. 


In  the  elimination  of  sodium  chloride  there  was  a  very  small  percentile 
change  when  dextrose  was  given  in  a  0.6  per  cent  solution  of  sodium-chloride 
and  a  much  greater  decrease  with  levulose  in  the  same  medium.  In  other 
words,  the  general  picture  indicates  that  the  transport  and  metabolism  of 
dextrose  were  specifically  different  from  those  of  levulose  as  regards  the 
equilibrium  of  sodium  chloride  and  the  volume  of  liquid  in  the  body.  One 
might  possibly  anticipate  here  an  hypothesis  which  will  be  discussed  later, 
namely,  that  a  dextrose  solution,  when  injected  rectally,  is  actually  utilized 
and  burned,  while  a  levulose  solution  is  stored  in  the  tissues  and  is  not 
metabolized  in  the  same  way  as  when  it  is  introduced  by  mouth.  (See  p.187.) 

The  alcohol  solution  brought  about  an  actual  increase  in  the  elimination 
of  urine,  but  not  a  corresponding  change  in  the  sodium  chloride  in  the  body. 
This  is  contrary  to  what  one  would  expect,  for,  since  alcohol  has  a  diuretic 
effect,  it  would  be  supposed  that  this  salt  would  be  washed  out  with  the  wa¬ 
ter.  Apparently,  however,  the  effect  of  alcohol  is  to  deprive  the  tissues  of 
water  and  to  cause  its  elimination  without  removing  other  constituents  at  the 
same  time.  Theoretically,  this  would  mean  an  actual  increase  in  the  con¬ 
centration  of  sodium  chloride  in  the  system.  It  is  evident  from  the  experi¬ 
mental  results  reported  here  that  the  problem  of  the  effect  of  the  rectal 
injection  of  various  substances  needs  considerable  further  study  in  regard  to 
the  volume  and  composition  of  the  urine  and  equilibrium  of  salts  and 
liquids  in  the  body.  It  is  conceivable  that  the  rectal  introduction  of  liquids 
containing  electrolytes  and  metabolites  may  present  an  entirely  different  set 
of  conditions  for  adjustment  in  the  matter  of  equilibrium  in  the  body  liquids 
from  those  with  the  same  liquids  introduced  by  mouth.  It  has  been  found, 
for  example,  that  the  introduction  of  sodium  bicarbonate  rectally  produces  a 
greater  change  in  the  hydrogen-ion  concentration  than  the  same  material 
introduced  intravenously.1  An  investigation  of  this  character  suggests  the 
opportunity  for  considerable  work  upon  the  difference  in  both  equilibrium 
and  metabolism  with  the  two  methods. 

RESPIRATORY  EXCHANGE  WITH  RECTAL 

INJECTION. 

One  of  the  main  purposes  of  this  whole  investigation  was  to  determine 
whether  or  not  alcohol  is  actually  utilized  when  introduced  rectally.  To 
this  end  it  was  necessary  to  find  whether  the  character  and  the  amount  of  the 
metabolism  were  affected  by  such  injection. 

The  respiratory  quotient  is  usually  considered  an  index  of  the  character  of 
the  material  utilized  in  the  body,  for  it  is  ordinarily  the  resultant  of  the  katab- 
olism  of  protein,  fat,  and  carbohydrate.  The  general  range  of  the  quotient 
is  from  0.71  for  fat  to  1.00  for  carbohydrate.  With  a  post-absorptive  sub¬ 
ject,  the  quotient  commonly  varies  between  0.75  and  0.90.  The  respiratory 
quotient  of  ethyl  alcohol  is  0.667,  so  that  when  a  considerable  amount  of  al¬ 
cohol  is  utilized  in  the  metabolism,  theoretically  it  tends  to  lower  the  quo¬ 
tient,  regardless  of  whether  it  replaces  but  one  substance  or  a  combination  of 
substances.  Replacement  of  fat  by  alcohol  lowers  the  quotient  least,  while 
the  replacement  of  carbohydrate  by  alcohol  lowers  it  most.  Accordingly, 
whatever  the  change  may  be  that  takes  place,  the  ultimate  effect  of  the  util- 


1Milroy:  Journ.  Physiol.,  1917,  51,  p.  281. 


RESPIRATORY  EXCHANGE. 


81 


ization  of  alcohol  in  the  metabolism  must  theoretically  be  a  lowering  of  the 
respiratory  quotient. 

When  various  foodstuffs  are  ingested  by  mouth,  there  is  nearly  always  an 
increase  in  the  total  metabolism  which  varies  with  the  kind  and  amount  of 
food  taken.  It  is  therefore  conceivable  that  alcohol  when  metabolized  will 
tend  to  raise  the  metabolism.  A  rise  or  a  lowering  of  the  metabolism  is 
usually  accompanied  by  a  similar  change  in  the  pulse-rate. 

The  problem  in  these  studies,  therefore,  was  to  determine,  by  measurement 
of  the  respiratory  exchange,  whether,  after  the  rectal  injection  of  alcohol,  the 
respiratory  quotient  indicated  that  alcohol  had  been  utilized  and  whether  the 
metabolism  had  been  stimulated,  also  to  note  whether  any  changes  in  the 
metabolism  were  accompanied  by  changes  in  pulse-rate. 

Sugars  are  substances  which  cause  a  rise  in  the  respiratory  quotient  when 
they  are  taken  by  mouth.  Levulose  and  sucrose  are  most  effective  in  this 
respect,  while  the  change  after  dextrose  depends  upon  the  previous  storage  of 
carbohydrates  in  the  body.  This  research  with  rectal  injection  was  there¬ 
fore  extended  to  include  studies  with  levulose  and  dextrose  to  find  if  their 
rectal  injection  produced  changes  in  the  respiratory  quotient  of  like  character 
and  magnitude  to  those  obtained  when  these  two  substances  are  taken  by 
mouth. 

Little  or  nothing  is  known  concerning  the  effect  upon  the  respiratory  ex¬ 
change  of  this  method  of  introduction  of  liquids  into  the  body,  i.  e.,  by  rec¬ 
tum.  Since  it  was  necessary  to  distinguish  between  the  influence  of  the 
method,  if  any,  and  the  effect  of  the  substance  injected,  studies  were  made  in 
which  different  volumes  of  a  weak  solution  of  sodium  chloride  (0.6  per  cent) 
were  injected  rectally.  These  experiments  served  a  double  purpose  in  that 
they  also  acted  as  a  control  upon  the  trend  of  the  respiratory  exchange  during 
the  period  of  the  day  in  which  most  of  the  alcohol  and  sugar  experiments 
were  made. 

The  general  plan  of  the  studies  of  respiratory  exchange  and  the  methods 
employed  have  already  been  outlined.  (See  p.  24.)  The  four  medical 
students  used  as  subjects,  A,  B,  C,  and  D,  have  likewise  been  described. 
(See  table  1,  p.  22.)  Subject  B  was  employed  only  in  the  experiments  with 
sodium  chloride  and  with  the  5  per  cent  alcohol  solution.  The  two  series 
with  this  subject  were  unsatisfactory  as  a  whole,  because  of  the  variability  of 
the  subject’s  temperament,  and  also  because  of  the  brevity  of  the  experi¬ 
ments.  The  results  of  these  observations  with  B  have  therefore  been 
omitted  from  the  discussion  of  the  respiratory  exchange,  although  his  data 
have  been  included  in  the  absorption  and  urine  studies. 

As  a  rule,  the  subjects  came  to  the  Laboratory  late  in  the  afternoon, 
either  without  food  since  breakfast  or,  in  the  later  experiments,  with  but  a 
light  lunch  at  midday.  After  the  preliminary  flushing  of  the  rectum  and  the 
lower  intestine,  the  minor  recording  appliances  were  adjusted  and  the  sub¬ 
ject  placed  himself  in  position  for  the  respiration  experiment.  For  the  most 
part  the  gasometer  method  of  measurement  was  used  (see  p.  24),  the  breath¬ 
ing  appliance  being  either  a  mouthpiece  or  a  mask.  The  former  appliance 
was  employed  only  in  the  earlier  experiments.  A  few  observations  were 
made  with  the  clinical  chamber  apparatus,  and,  for  comparison,  experiments 
were  also  carried  out  in  which  the  substance  under  investigation  was  given 
orally. 


82 


HUMAN  METABOLISM  WITH  ENEMATA. 


Observations  of  the  respiratory  exchange  and  pulse-rate  were  usually  made 
previous  to  the  injection  to  provide  basis  for  comparison,  as  well  as  during 
and  following  the  giving  of  the  solution.  Occasionally  the  preliminary  pe¬ 
riods  were  omitted  in  order  that  the  study  might  be  continued  for  a  greater 
length  of  time  after  the  injection  without  fatiguing  the  subject. 

In  presenting  the  results,  the  general  details  as  to  volume  of  solution,  dura¬ 
tion  of  injection,  and  periods  before  and  after  the  beginning  of  the  injection 
are  given  in  tables  for  the  individual  series.  The  experimental  data  appear 
in  the  form  of  curves  indicating  for  each  experiment  the  general  course  of  the 
respiratory  quotient,  the  oxygen  consumption  per  minute,  and  the  pulse-rate 
per  minute.  These  charts  show  the  level  of  the  three  factors  in  the  different 
periods  of  the  experiments  before  and  after  the  beginning  of  the  rectal  in¬ 
jection. 

When  the  mask  was  used  it  was  possible  to  make  continuous  observations, 
this  being  clearly  shown  by  the  unbroken  curves.  The  interruptions  in  these 
curves  which  occasionally  occur  are  usually  due  to  a  temporary  discontinu¬ 
ance  of  the  observations  for  urination,  and  infrequently  to  slight  adjustments 
of  some  of  the  appliances.  Whenever  the  sleep  recorder  was  used,  the  trac¬ 
ing  is  usually  reproduced  in  the  figure  for  assistance  in  interpreting  the 
various  changes  in  the  three  factors.  The  variation  in  the  amount  of  sleep 
of  the  subjects  was  a  disturbing  feature  of  these  studies  and  frequently 
obscured  the  true  effect  of  the  injection. 

The  number  of  periods1  before  injection  recorded  in  the  tables  includes  all 
those  in  which  measurements  were  made.  In  several  of  the  charts,  however, 
only  those  periods  in  the  half  hours  immediately  preceding  the  beginning  of 
the  injection  are  plotted.  In  some  cases,  the  subject  was  not  allowed  the 
customary  half  hour  of  rest  before  the  initial  measurement,  but  the  experi¬ 
ment  was  begun  as  soon  as  the  man  lay  down.  The  metabolism  of  the 
subject  was  not  therefore  at  a  standard  level,  and  there  was  usually  an  imme¬ 
diate  sharp  decline  in  the  oxygen  absorption  and  pulse-rate  in  the  first  por¬ 
tion  of  the  experiment,  due  to  the  cessation  of  the  previous  muscular  activity. 

The  volume  of  the  solution  measured  out  from  the  general  source  of  supply 
for  injection  was  generally  about  20  c.  c.  more  than  the  volume  actually  in¬ 
jected,  this  20  c.  c.  representing  the  liquid  usually  remaining  in  the  catheter 
and  connections  at  the  conclusion  of  the  injection.  The  total  volumes  meas¬ 
ured  are  given  in  the  tables  as  the  amount  injected,  but  correction  is  made 
for  the  residue  when  calculating  the  amount  absorbed. 

In  discussing  the  results,  the  experiments  with  the  sodium-chloride  solu¬ 
tion  are  first  considered,  those  with  the  alcohol  solutions  in  the  various  con¬ 
centrations  are  next  presented,  and  finally  those  with  the  two  sugars,  dextrose 
and  levulose. 

1  The  word  “period”  is  used  to  designate  the  smallest  division  of  time  for  which  results  were  ob¬ 
tained.  An  “experiment”  consists  of  one  or  more  “periods”  following  one  another  at  short 
intervals,  as  in  the  experiments  with  the  mouthpiece,  or  succeeding  one  another  without 
interval,  as  in  the  experiments  with  the  mask. 


RESPIRATORY  EXCHANGE  WITH  SODIUM  CHLORIDE. 


83 


RESPIRATORY  EXCHANGE  WITH  RECTAL  INJECTION  OF  A 

SOLUTION  OF  SODIUM  CHLORIDE. 

The  solution  used  in  the  sodium-chloride  experiments  was  the  same  as  that 
employed  as  a  carrier  for  the  sugars,  i.  e.,  a  0.6  per  cent  concentration  of  so¬ 
dium  chloride  in  water.  Such  a  solution  is  a  common  medium  for  the  rectal 
introduction  of  various  substances.  A  large  amount  of  the  material  was 
made  up  at  the  beginning  of  the  observations  and  stored,  this  being  drawn 
upon  as  needed  for  the  individual  experiments.  Both  the  gasometer  method 
and  the  clinical  respiration  chamber  were  used  in  studying  the  effect  of  rectal 
injection  of  a  sodium-chloride  solution. 

Sodium-Chloride  Experiments  with  Gasometer  Method. 

In  the  gasometer  series  there  were  14  experiments  (excluding  those  with 
subject  B),  of  which  8  were  with  subject  A,  5  with  subject  C,  and  1  with  sub¬ 
ject  D.  The  general  data  for  these  experiments  are  presented  in  table  21, 
and  the  results  of  the  observations  are  given  graphically  in  figures  5  to  18 . 


Table  21. — Statistics  of  respiratory  exchange  observations  before  and  after  the  injection  by  rectum 

of  a  0.6  per  cent  solution  of  sodium  chloride. 


Subject. 

Date. 

Amount 

injected. 

Duration 

of 

injection. 

Periods  before 
injection. 

Periods  after 
injection. 

Number. 

Time 

covered. 

Number. 

Time 

covered. 

1915 

c.  c. 

min. 

h. 

min. 

h. 

min. 

A 

Oct.  la 

100 

#  . 

3 

0 

45 

12 

2 

32 

200 

#  # 

9 

2 

29 

6 

0 

58 

Oct.  15° 

300 

8 

4 

0 

45 

11 

3 

8 

Oct.  19° 

325 

8 

4 

0 

53 

13 

2 

49 

Nov.  4a 

420 

%  # 

4 

1 

17 

11 

2 

38 

Dec.  8b 

520 

23 

6 

1 

00 

24 

3 

30 

Dec.  206 

500 

12 

11 

2 

8 

15 

2 

9 

1916 

Mar.  146 

260 

17 

8 

1 

20 

16 

2 

40 

Mar.  206 

260 

28 

10 

1 

48 

10 

1 

42 

1915 

C 

Oct.  16° 

320 

2 

5 

1 

6 

6 

1 

21 

Oct.  21° 

320 

4 

5 

1 

15 

8 

2 

4 

Nov.  2° 

420 

5 

5 

1 

8 

11 

2 

45 

1916 

Feb.  21 6 

520 

30 

9 

1 

29 

11 

1 

51 

Mar.  16& 

260 

25 

7 

1 

10 

11 

1 

50 

D 

Apr.  14 6 

500 

27 

8 

1 

17 

13 

2 

13 

°  The  mouthpiece  and  gasometer  combination  was  used,  with  the  subject  sitting. 
The  mask  and  gasometer  combination  was  used,  with  the  subject  lying  on  a  couch. 


In  the  experiment  with  A  on  October  1,  two  injections  were  given  on  the 
same  evening,  but  these  were  separated  by  a  considerable  interval  of  time 
(1  hour  45  minutes).  The  period  of  flow,  which  represents  the  time  from  the 
beginning  of  the  injection  until  its  conclusion,  varied  from  2  to  30  minutes. 
In  a  number  of  the  first  experiments,  the  actual  time  of  flow  was  not  recorded, 


84 


HUMAN  METABOLISM  WITH  ENEMATA. 


but  as  the  period  of  introduction  was  short  in  these  earlier  observations,  it  is 
probable  that  the  injection  was  completed  in  5  minutes  or  less.  With  alcohol 
and  the  sugars,  slower  rates  of  rectal  alimentation  were  adopted  in  the  later 
observations;  consequently,  the  same  procedure  was  followed  in  the  later  ex¬ 
periments  with  the  solution  of  sodium  chloride.  The  measurements  of  the 
respiratory  exchange  were  not  made  continuously  until  the  experiment  with 
A  on  December  8,  which  was  the  first  experiment  in  the  sodium-chloride 
series  in  which  the  mask  was  used  as  a  breathing  appliance.  Accordingly,  in 
the  earlier  experiments  the  average  length  of  the  period  may  not  be  found  by 
dividing  the  length  of  time  by  the  number  of  periods.  The  average  number 
of  periods  before  injection  in  the  sodium-chloride  series  was  6  and  the  average 
time  covered  was  1  hour  and  20  minutes.  The  average  number  of  periods 
after  the  beginning  of  the  injection  was  12  and  the  average  length  of  time 
covered  was  2  hours  and  17  minutes.  The  sleep-recording  apparatus  was 
used  in  the  experiment  with  C  on  February  21,  1916,  and  in  the  subsequent 
experiments  with  all  of  the  subjects  in  March  and  April  1916. 

The  sodium-chloride  experiments  were  conducted  primarily  as  controls  to 
give  results  which  should  serve  as  a  basis  of  comparison  for  the  results  of  ob¬ 
servations  in  which  alcohol,  dextrose,  and  levulose  were  injected  into  the 
rectum.  The  three  factors  particularly  observed  were  (1)  the  oxygen  con¬ 
sumption  as  a  measure  of  the  total  metabolism;  (2)  the  pulse-rate  for  its 
significance  in  relation  to  changes  in  the  total  metabolism,  as  well  as  the 
effect  upon  it  of  the  solution;  and  (3)  the  respiratory  quotient  as  an  indicator 
of  the  utilization  of  the  material  injected.  Since  theoretically  the  sodium- 
chloride  solution  should  produce  no  change  that  would  not  take  place  if  no 
injection  were  made,  any  changes  which  might  occur  in  these  three  factors 
after  the  introduction  of  the  solution  should  be  taken  into  consideration  in 
interpreting  results  obtained  after  the  introduction  of  the  other  materials 
employed  in  this  research,  and  especially  those  in  which  a  sodium-chloride 
solution  was  used  as  a  carrier. 

Most  of  the  difficulties  encountered  in  securing  comparable  results  in  this 
series  were  due,  first,  to  the  use  of  short  periods  which  were  not  continuous, 
and  second,  to  the  varying  conditions  as  to  sleep.  The  latter  had  an  effect 
upon  the  metabolism,  particularly  in  relation  to  the  respiratory  quotient,  but 
unfortunately  the  apparatus  for  detecting  sleep  was  not  applied  until  the  re¬ 
search  was  more  than  half  completed.  Accordingly,  as  most  of  the  experi¬ 
ments  with  the  solution  of  sodium  chloride  were  made  before  this  apparatus 
was  introduced,  but  little  data  could  be  had  in  this  series  as  to  the  amount  of 
sleep  and  its  effect  upon  the  metabolism.  Subject  A,  particularly,  became 
drowsy  even  in  the  early  experiments,  when  he  was  in  the  sitting  position, 
and  it  was  repeatedly  necessary  to  urge  him  to  keep  awake.  In  spite  of  this 
he  frequently  fell  asleep  or  was  very  drowsy,  so  that  the  ventilation  data  were 
in  many  cases  extremely  low.  Undoubtedly,  also,  the  change  from  being 
awake  at  the  beginning  of  the  observations  to  sleep  near  the  end  affected  the 
respiratory  quotient. 

The  results  obtained  may  be  considered  first  from  the  standpoint  of  general 
level  of  metabolism  as  compared  with  the  basal  metabolism  of  the  individual. 
(See  table  1,  p.  22.)  This  concerns  the  values  obtained  before  rectal  injection 
began.  Second,  the  results  may  be  considered  from  the  standpoint  of  the 
change  in  the  metabolism  which  took  place  after  rectal  injection  began,  and 


RESPIRATORY  EXCHANGE  WITH  SODIUM  CHLORIDE. 


85 


this  may  be  compared  to  the  metabolism  in  the  periods  preceding  injection. 
The  succeeding  portions  of  time  after  injection  may  also  be  compared  with 
one  another.  This  latter  method  is  necessary  in  some  of  the  experiments, 
because  there  were  no  periods  before  rectal  injection  took  place. 

The  conditions  under  which  these  experiments  were  made  differ  in  several 
ways  from  the  usual  measurements  of  the  “ basal  ”  metabolism.  In  the  first 
place,  the  subject  was  not  in  a  strictly  post-absorptive  condition,  because  the 
first  observations  were  begun  earlier  than  12  hours  after  the  last  food.  As 
previously  pointed  out  (see  p.  81),  at  the  beginning  of  the  series  the  subjects 
had  their  last  meal  in  the  morning,  i.  e.,  breakfast.  In  some  cases,  however, 
they  departed  from  this  requirement  and  took  food  later  than  the  usual 
breakfast  time,  e.  g.,  October  15,  10h  00m  a.  m.;  October  19,  10h  30m  a.  m.; 
December  20,  9h  30m  a.  m.  Later  in  the  research  they  were  allowed  to  have 
food  (a  lunch)  at  noon,  as  it  was  believed  that  a  light  lunch  at  that  time  would 
not  have  an  effect  upon  the  metabolism  at  5h  30m  p.  m.,  about  which  time 
the  first  measurements  began.  In  general,  the  latest  time  that  food  was 
taken  was  at  lh  30m  p.  m.  Subject  C  on  March  16  had  a  small  portion  of 
apple  at  2h  20m  p.  m. 

The  second  unusual  condition  was  the  time  of  beginning  the  preliminary 
or  base-line  measurements,  this  being  in  the  latter  part  of  the  afternoon 
instead  of  in  the  morning,  as  is  the  usual  procedure.  During  the  day  the 
subjects  were  occupied  in  their  usual  attendance  at  clinics  and  lectures  and 
in  similar  activities  incidental  to  the  regular  routine  of  a  medical  student. 
When  they  came  to  the  Laboratory  they  were,  as  a  rule,  more  or  less  fatigued 
and  quite  ready  for  a  rest.  Their  mental  condition  also  varied  according  to 
whether  the  day’s  work  had  been  one  of  unusual  interest,  dry  routine,  or 
diversified  in  character.  In  the  observations  reported  by  Benedict 1  on  a 
fasting  man,  the  values  for  the  oxygen  consumption  between  7h  00m  and 
7h  45m  p.  m.  on  the  twelfth  to  the  thirtieth  days  of  the  fast  were  all  higher 
than  those  obtained  in  the  morning  between  8h  30m  and  9h  30m  a.  m.,  the 
increase  varying  from  1.5  per  cent  to  10  per  cent,  the  usual  increase  being 
about  6  per  cent.  The  course  of  the  metabolism  between  5h  30m  and 
10h  30m  p.  m.  with  the  subjects  of  the  rectal  study  could  not  be  predicted. 

Another  condition  which  differed  from  those  of  most  previous  work  in 
the  measurement  of  respiratory  exchange  was  that  instead  of  making  single 
isolated  periods  of  measurement,  it  was  almost  invariably  the  case  that  two 
and  often  more  periods  of  5  to  10  minutes’  duration  were  carried  out  im¬ 
mediately  following  one  another  without  an  interval  between  periods.2 
This  was  the  usual  procedure  in  those  experiments  in  which  the  mouthpiece 
was  used.  After  3  to  5  periods  of  measurement  there  was  an  interval  which 
varied  in  length,  but  was  usually  about  30  minutes,  and  then  3  more  measure¬ 
ments  were  made  in  the  same  way.  When  the  mask  was  used,  the  periods 
succeeded  one  another  without  interruption  from  the  beginning  to  the  end 
of  the  experiment.  The  individual  periods  varied  from  4  to  15  minutes  in 
duration. 

In  metabolism  measurements  as  usually  made  there  is  a  single  period  of 
observation  varying  in  length  between  5  and  15  minutes,  and  then  an  interval 

‘Benedict:  Carnegie  Inst.  Wash.  Pub.  No.  203,  1915,  p.  334. 

2 Higgins  (Am.  Journ.  Physiol.,  1916,  41,  p.  258),  in  this  Laboratory,  carried  out  a  number  of  experi¬ 
ments  with  alcohol  and  sugars  in  which  four  successive  periods  in  15  minutes  were  made  with¬ 
out  interruption. 


86 


HUMAN  METABOLISM  WITH  ENEMATA. 


of  rest  before  the  next  period.  With  such  a  routine  there  is  no  means  of 
knowing  whether  in  the  rest  interval  the  metabolism  is  the  same,  either  in 
character  or  in  amount,  as  in  the  observation  itself.  It  is  barely  possible 
that  the  subject  may  rouse  himself  to  the  same  degree  or  maintain  the  same 
degree  of  relaxation  in  each  of  the  observation  periods,  but  during  the 
intervals  his  condition  of  tenseness  or  relaxation,  wakefulness,  and  attention 
may  be  quite  different  from  that  in  the  periods  themselves.  Johansson  1 
recognized  that  it  is  not  feasible  for  a  subject  to  maintain  a  uniform  condition 
of  complete  muscular  rest  for  any  great  length  of  time.  His  usual  routine 
was  to  have  a  half  hour  or  an  hour  of  complete  muscular  rest  during  which 
the  metabolism  measurements  were  made,  followed  by  a  half  hour  or  an  hour 
in  which  the  subject  was  permitted  to  move  about  to  some  extent;  then  an¬ 
other  experimental  period  was  carried  out. 

Even  with  the  best  conditions  of  experimental  technique,  there  may  be 
considerable  variation  from  period  to  period  when  the  experiments  consist 
of  isolated  periods.  This  was  evident  in  a  study  of  the  respiratory  exchange 
of  17  untrained  medical  students.2  Twelve  measurements  of  10  to  15 
minutes’  duration  followed  each  other  in  the  morning,  with  the  subject  in 
the  post-absorptive  condition  and  with  intervals  of  at  least  5  minutes  be¬ 
tween  the  periods.  The  purpose  of  the  study  was  to  compare  the  respiratory 
exchange  obtained  with  the  Benedict  portable  apparatus  3  with  that  obtained 
from  the  collection  of  the  expired  air  in  a  gasometer  4  and  its  analysis. 
Three  different  breathing  appliances  (mouthpiece,  nosepieces,  and  mask) 
were  used.  The  main  variation  was,  therefore,  in  the  techniques  used  in 
the  different  periods.  With  an  average  oxygen  consumption  of  236  c.  c., 
the  differences  between  the  maximum  and  minimum  oxygen  consumption 
for  the  12  periods  varied  with  the  17  subjects  from  12  to  78  c.  c.  per  minute, 
with  an  average  difference  of  33  c.  c.  per  minute.5 6  The  variations  were  not 
always  due  to  differences  in  technique,  as  frequently  wide  differences  in 
oxygen  consumption  were  found  with  the  same  apparatus  and  breathing 
appliance.  Also,  they  were  not  due  to  the  varying  amount  of  sleep  or 
drowsiness,  as  the  signal-magnet  stimulus  was  used  in  every  period,  to  which 
they  responded  regularly. 

If  there  are  such  variations  from  period  to  period  when  the  measurements 
are  isolated,  it  is  all  the  more  likely  that  there  will  be  variations  of  the  same 
or  greater  magnitude  when  they  are  made  continuously  over  short  intervals 
of  time  without  lapses.  The  shorter  the  unit  of  time  and  the  longer  the 
series,  the  less  likelihood  there  is  of  absolute  constancy  in  a  physiological 
process  set  about  with  so  many  variables  as  may  exist  in  higher  biological 
organisms,  such  as  humans.  This  is  axiomatic.  The  important  point  in 
regard  to  the  experiments  here  is  that  with  the  mouthpiece  there  was  usually 
a  series  of  three  or  more  periods  in  succession,  and  that  with  the  mask  the 
entire  experiment  of  several  hours’  duration  was  generally  an  uninterrupted 
series  of  periods  varying  in  length  from  5  to  15  minutes.  With  the  latter 
appliance  the  metabolism  of  the  subject  was  therefore  being  measured  in 


Johansson:  Skand.  Arch.  f.  Physiol.,  1908,  21,  p.  1. 

2  Hendry,  Carpenter,  and  Emmes:  Boston  Med.  and  Surg.  Journ.,  1919,  181,  pp.  285,  334,  and  368. 

5  Benedict:  Boston  Med.  and  Surg.  Journ.,  1918,  178,  p.  667. 

4  Tissot:  Journ.  de  physiol,  et  de  pathol.  gen.,  1904,  6,  p.  688;  Carpenter,  Carnegie  Inst.  Wash.  Pub. 

No.  216,  1915,  p.  63. 

6 Hendry,  Carpenter,  and  Emmes:  loc.  cit.,  p.  342,  table  vii. 


RESPIRATORY  EXCHANGE  WITH  SODIUM  CHLORIDE.  87 

such  a  manner  as  to  show  all  the  variations  that  may  occur  over  a  fairly 
long  period  of  time. 

RESULTS  OF  MEASUREMENTS  BEFORE  RECTAL  INJECTION. 

Pulse-Rate. 

Subject  A. — The  results  of  the  observations  on  the  pulse-rate  in  the  mouth¬ 
piece  experiments  with  subject  A  are  shown  in  figures  5  to  8.  On  all  of  these 
days  there  was  a  preliminary  rest  period  of  at  least  a  half  hour  in  which  no 
observations  were  made  of  the  metabolism.  During  this  period  the  pulse- 
rate  was  recorded,  but  these  values  are  not  plotted  on  the  charts.  During 
the  last  15  to  25  minutes  of  this  preliminary  rest  period  there  was  little  or  no 
change  in  pulse-rate.  In  two  of  the  experiments,  October  1  and  November 
4,  there  was  a  noticeable  fall  in  rate  in  the  first  three  experimental  periods 
preceding  the  injection,  and  in  all  of  the  experiments  the  pulse-rate  in  the 
period  at  or  immediately  preceding  the  rectal  injection  was  materially  lower 
than  that  during  the  initial  periods  of  the  experiments.  It  is  therefore 
evident  that  a  half-hour  preliminary  rest  was  not  sufficient  for  the  pulse-rate 
to  reach  a  basal  level  at  this  period  of  the  day,  or  that  there  was  a  factor  in 
the  experiments  which  tended  to  lower  the  heart-rate.  This  factor  was 
probably  either  drowsiness  or  the  quieting  effect  of  the  relaxed  condition 
during  the  experimental  periods.  The  pulse-rate  just  before  the  injection 
varied  from  49  beats  on  November  4  to  70  beats  on  October  19.  None  of 
these  experiments  were  in  the  morning  and  the  subject  was  not  in  a  strictly 
post-absorptive  condition. 

The  routine  in  the  experiments  with  the  mask  in  December  1915  and  March 
1916  (see  figs.  9  to  12)  differed  from  those  with  the  mouthpiece  in  that  there 
was  practically  no  preliminary  rest,  and  the  measurements  commenced  as 
soon  as  the  subject  lay  down.  As  shown  in  table  21,  the  preliminary  portion 
(before  injection)  was  over  an  hour  in  length.  In  the  figures  only  the  40 
minutes  (4  periods)  preceding  the  rectal  injection  are  plotted,  so  that  the 
average  value  indicated  for  the  first  period  in  the  figures  is  at  least  one-half 
hour  after  the  subject  lay  down.  On  March  14  and  20  (see  figs.  11  and  12) 
it  is  evident  from  the  sleep  record  that  the  man  was  asleep  practically  the 
entire  experiment.  On  December  20  the  protocols  show  that  he  was  alter¬ 
nately  asleep  and  awake  during  the  preliminary  observations.  The  pulse- 
rates  varied  between  58  and  66  beats  in  the  periods  immediately  preceding 
the  rectal  injection  and,  in  general,  the  preliminary  curves  are  less  variable 
than  those  in  the  experiments  with  the  mouthpiece.  The  basal  pulse-rate 
(see  table  1,  p.  22)  for  this  man  was  64  beats  per  minute,  so  that  the  rates 
obtained  in  this  series  are  close  to  this  value. 

Subject  C. — The  pulse-rates  for  the  mouthpiece  experiments  with  subject 
C  are  shown  in  figures  13  to  15.  The  rates  at  or  immediately  preceding  the 
rectal  injection  vary  between  64  and  80  beats.  The  experiment  on  October 
16  was  in  the  early  afternoon.  The  other  two  were  in  the  early  evening. 
In  all  three  experiments  a  half-hour  rest  period  preceded  the  metabolism 
observations.  The  pulse-rates  with  this  subject  were  more  nearly  uniform 
than  those  of  subject  A.  In  the  two  1916  experiments  with  the  mask  (see 
figs.  16  and  17)  the  preliminary  periods  continued  for  more  than  an  hour, 
and  the  original  protocols  show  that  in  each  experiment  there  was  some 
sleep.  In  the  period  immediately  preceding  the  rectal  injection,  the  values 


88 


HUMAN  METABOLISM  WITH  ENEMATA. 


SUBJECT  A.  OCT.  15.  1915 


175 

65 

60 

55 


n 

IRATOR^ 

'  QUOT 

J  ' 

.  "  ntor 
*s. 

IENT 

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zr* 

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n  pf 

R  MINU 

u 

•  c,  o.  c.  - 

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i  PER  b 

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X. _ 

- ** 

HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 

5 


4  5  6 

HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 

6 


Fig.  5. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  October  1,  1915, 
before  and  after  rectal  injection  of  100  c.  c.  of  a  0.6  per  cent  solution  of  sodium  chloride, 
followed  by  a  second  injection  of  200  c.  c.  (Mouthpiece,  with  intermittent  observation.) 

The  solid  portions  of  the  three  curves  represent  the  averages  for  the  periods  and  the  broken 
portions  the  intervals  between  observations.  This  applies  to  all  subsequent  experiments 
with  the  mouthpiece.  The  two  heavy  vertical  lines  indicate  the  beginning  of  the  first  and 
second  rectal  injections. 

Fig.  6. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  October  15,  1915, 
before  and  after  rectal  injection  of  300  c.c.  of  a  0.6  per  cent  solution  of  sodium  chloride. 
(Mouthpiece,  with  intermittent  observation.) 


SUBJECT  A.  OCT  19.  1915 


SUBJECT  A.  NOV  4.  1915 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 

7 


8 


Fig.  7. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  October  19,  1915, 
before  and  after  rectal  injection  of  325  c.  c.  of  a  0.6  per  cent  solution  of  sodium  chloride. 
(Mouthpiece,  with  intermittent  observation.) 

Fig.  8. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  November  4,  1915, 
before  and  after  rectal  injection  of  420  c.  c.  of  a  0.6  per  cent  solution  of  sodium  chloride. 
(Mouthpiece,  with  intermittent  observation.) 


RESPIRATORY  EXCHANGE  WITH  SODIUM  CHLORIDE. 


89 


SUBJECT  A.  DEC.  20.  1915 


9 


10 


Fig.  9. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  December  8,  1915, 
before  and  after  rectal  injection  of  520  c.  c.  of  a  0.6  per  cent  solution  of  sodium  chloride. 
(Mask,  with  continuous  observation.) 

Fig.  10. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  December  20, 
1915,  before  and  after  rectal  injection  of  500  c.  c.  of  a  0.6  per  cent  solution  of  sodium  chloride. 
(Mask,  with  continuous  observation.) 


SUBJECT  A.  MAR  14.  1916 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


SUBJECT  A.  MAR.  20.  1916  MASK 
260  c.c.  NaCl  SOLUTION  (0.6p.  ct) 


HALF  HOURS  AFTER  RECTAL, 
INJECTION  BEGAN 


11 


12 


Fig.  11. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A, 
March  14,  1916,  before  and  after  rectal  injection  of  260  c.  c.  of  a  0.6  per  cent 
solution  of  sodium  chloride.  (Mask,  with  continuous  observation.) 

The  horizontal  line  at  the  bottom  of  this  and  subsequent  charts  gives  a  record 
of  sleep,  the  solid  portions  indicating  when  the  subject  was  asleep,  and  the 
broken  portions  when  he  was  awake. 

Fig.  12. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A, 
March  20,  1916,  before  and  after  rectal  injection  of  260  c.  c.  of  a  0.6  per  cent 
solution  of  sodium  chloride.  (Mask,  with  continuous  observation.) 


90 


HUMAN  METABOLISM  WITH  ENEMATA. 


8UBJECT  C.  OCT  21.  1915 


SUBJECT  C.OCT  10.  1915 


075 


RpCjplp  ATOP 

♦jlOUTHP 

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L, 

L. 

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JTE,  c.  o. 

— r—  "  . 

— 

PULSE  PER 

JIINUT.E 

l— Tnz; 

0 

2 

HALF  HOURS  AFTER 
RECTAL  INJECTION  BEGAN 

13 


0.85 

0.80 


-  p— ! 

DTIENT 

- 

CLi 

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L 

02  PER  Mil 

IUTE,  c. 

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PULSE  PEF 

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HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 

14 


Fig.  13. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  C,  Oc¬ 
tober  16,  1915,  before  and  after  rectal  injection  of  320  c.  c.  of  a  0.6  per  cent 
solution  of  sodium  chloride.  (Mouthpiece,  with  intermittent  observation.) 

Fig.  14. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  C,  Oc¬ 
tober  21, 1915,  before  and  after  rectal  injection  of  320  c.  c.  of  a  0.6  per  cent 
solution  of  sodium  chloride.  (Mouthpiece,  with  intermittent  observation.) 


SUBJECT  C.  FEB.  21.  1916 

520  c.  c.  NaCI  SOLUTION  (0.6  p.  ct) 


MASK 


15 


16 


Fig.  15. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  C,  November  2, 1915, 
before  and  after  rectal  injection  of  420  c.  c.  of  a  0.6  per  cent  solution  of  sodium  chloride. 
(Mouthpiece,  with  intermittent  observation.) 

Fig.  16. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  C,  February  21,  1916, 
before  and  after  rectal  injection  of  520  c.  c.  of  a  0.6  per  cent  solution  of  sodium  chloride. 
(Mask,  with  continuous  observation.) 


were  64  and  68  beats.  The  basal  pulse-rate  (see  table  1,  p.  22)  for  this  sub¬ 
ject  was  65  beats  per  minute. 

Subject  D. — There  was  only  one  control  experiment  with  subject  D.  The 
observations  began  about  15  minutes  after  the  subject  lay  down  and  are 
plotted  in  full  in  the  curve.  (See  fig.  18.)  There  was  a  period  of  sleep  of 
approximately  30  minutes  which  produced  a  marked  depression  in  the  pulse- 
rate,  making  it  difficult  to  compare  the  values  obtained  before  and  after 


RESPIRATORY  EXCHANGE  WITH  SODIUM  CHLORIDE. 


91 


rectal  injection.  At  the  time  rectal  injection  began,  the  pulse-rate  was  79 
beats  per  minute. 

Oxygen  Absorption. 

Subject  A. — In  the  mouthpiece  experiments  with  subject  A  (figs.  5  to  8),  the 
greatest  range  in  the  oxygen  absorption  (29  c.  c.)  was  on  October  15.  The 
averages  for  the  four  experiments  are  chronologically  202,  201,  205,  and  197 
c.  c.  The  basal  oxygen  absorption  for  this  subject  was  206  c.  c.  per  minute. 
(See  table  1,  p.  22.)  In  the  four  experiments  with  the  mask  (figs.  9  to  12) 
there  were  large  fluctuations  in  the  oxygen  absorption.  The  values  on 
December  20  (fig.  10)  appear  unreasonable  because  they  are  so  low,  even  on 
the  average  (166  c.  c.),  and  the  pre-injection  value  of  186  c.  c.  near  the  begin¬ 
ning  of  the  experiment  was  probably  nearer  the  truth.  The  pre-injection 

SUBJECT  O.  APR.  t4.  191® 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN  HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


17  18 

Fig.  17. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  C,  March  16,  1916, 
before  and  after  rectal  injection  of  260  c.  c.  of  a  0.6  per  cent  solution  of  sodium  chloride. 
(Mask,  with  continuous  observation.) 

Fig.  18. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  D,  April  14,  1916, 
before  and  after  rectal  injection  of  500  c.  c.  of  a  0.6  per  cent  solution  of  sodium  chloride. 
(Mask,  with  continuous  observation.) 


averages  for  the  plotted  periods  in  the  other  mask  experiments  are  199,  214, 
and  215  c.  c.  As  will  be  brought  out  more  fully  in  the  discussion  of  the 
respiratory  quotient,  the  picture  on  March  20  corresponds  to  that  after  a 
carbohydrate  meal. 

Subject  C. — Subject  C  did  not  vary  so  widely  in  his  oxygen  absorption 
from  period  to  period  as  did  A,  although  the  values  were  by  no  means  uni¬ 
form.  The  averages  for  the  periods  previous  to  injection  in  the  mouthpiece 
experiments  (figs.  13  to  15)  were  296,  312,  and  277  c.  c.  per  minute,  a  rather 
wide  range.  On  October  21  the  oxygen  absorption  was  high  and  accompa¬ 
nied  by  a  high  pulse-rate — 79  beats.  The  basal  oxygen  value  for  this  sub¬ 
ject  was  285  c.  c.  per  minute.  (See  table  1,  p.  22.)  The  variations  in  the  pre¬ 
liminary  oxygen  values  in  the  two  experiments  with  the  mask  (figs.  16  and  17) 
were  41  c.  c.  and  23  c.  c.,  and  the  averages  for  the  four  periods  immediately 


92 


HUMAN  METABOLISM  WITH  ENEMATA. 


preceding  the  injection  were  253  and  273  c.  c.  per  minute.  In  both  experi¬ 
ments  there  was  a  short  interval  of  sleep  which  tended  to  depress  the  values 
slightly. 

Subject  D. — In  the  one  experiment  with  subject  D  (fig.  18),  there  was  some 
fluctuation  in  the  first  three  periods  which  were  followed  by  five  periods  in 
succession  with  a  narrow  range  of  but  17  c.  c.  The  average  oxygen  absorp¬ 
tion  for  these  five  periods  was  250  c.  c.  per  minute.  No  basal  values  are 
available  for  this  subject. 

Respiratory  Quotient. 

Subject  A. — The  respiratory  quotients  in  the  four  mouthpiece  experiments 
with  subject  A  were  extremely  variable  from  period  to  period  before  rectal 
injection  began,  the  greatest  range  being  0. 1 1  on  October  19.  Excluding  the 
experiment  of  October  1,  the  average  values  for  the  periods  before  injection 
were  normal,  being  0.84,  0.80,  and  0.81.  The  respiratory  quotients  in  the 
four  experiments  with  the  mask  show  a  marked  degree  of  variability,  al¬ 
though  not  so  great  as  with  the  mouthpiece.  The  average  values  for  the  four 
periods  before  injection  were  0.81,  0.79,  0.81,  and  0.87,  the  latter  occurring  on 
March  20.  The  whole  picture  of  the  last  experiment  (fig.  12)  indicates  the 
ingestion  of  a  heavy  carbohydrate  meal  before  the  experiment  began,  al¬ 
though  the  subject  reported  that  the  last  food  taken  was  4  hours  before  he 
came  to  the  Laboratory.  This  consisted  of  broth,  mashed  potatoes,  fish, 
graham  bread,  and  coffee. 

Subject  C. — In  the  three  experiments  with  the  mouthpiece,  the  range  of 
quotients  was  much  narrower  than  with  subject  A.  The  average  values  for 
the  preliminary  observations  were  0.77,  0.83,  and  0.80.  In  the  two  experi¬ 
ments  with  the  mask,  the  figures  before  rectal  injection  were  markedly  influ¬ 
enced  by  the  period  of  sleep  which  occurred.  This  caused  a  wide  range,  viz, 
approximately  0.10  in  both  experiments.  The  average  of  the  two  periods 
just  before  injection  began  is  0.83  for  both  days. 

Subject  D. — The  range  of  values  before  injection  took  place  in  the  single 
control  experiment  with  subject  D  was  rather  wide,  viz,  0.10,  this  being  due 
to  sleep.  The  value  nearest  to  the  time  injection  took  place  was  0.81. 

General  Conclusions. 

To  sum  up,  the  measurements  of  the  pulse-rate,  oxygen  consumption,  and 
respiratory  quotient  of  the  three  subjects  A,  C,  and  D  before  rectal  injection 
took  place  show  first  that  one  of  the  subjects,  A,  gave  extremely  variable 
results  from  period  to  period  in  the  same  experiments,  but  the  average  of  all 
the  periods  in  any  single  experiment  is  not  far  from  those  of  the  other  experi¬ 
ments  and  reasonably  close  to  the  basal  value  for  this  subject.  Subject  C 
gave  less  variable  results  in  the  individual  experiments,  but  widely  varying 
results  among  the  different  experiments.  There  was  only  one  experiment 
with  D.  The  causes  for  these  variations  are  considered  to  be:  (1)  inconstancy 
of  subject  A;  and  (2)  the  conditions  under  which  these  experiments  were 
carried  out,  viz,  (a)  in  the  evening,  ( b )  with  varying  conditions  as  to  the  sub¬ 
ject  himself,  and  (c)  the  use  of  consecutive  measurements  in  groups  of  periods 
rather  than  measurements  in  single  isolated  periods.  The  effect  of  the  rectal 
injection  of  sodium-chloride  solution  therefore  has  to  be  considered  with 
respect  to  the  course  of  the  individual  experiments  and  not  with  respect  to 
the  average  of  all  the  experiments. 


RESPIRATORY  EXCHANGE  WITH  SODIUM  CHLORIDE.  93 


RESULTS  OF  MEASUREMENTS  AFTER  RECTAL  INJECTION  OF  SODIUM 

CHLORIDE. 

Pulse-Rate. 

In  all  of  the  four  mouthpiece  experiments  with  subject  A  (figs.  5  to  8) 
there  was  a  falling  pulse-rate  throughout  most  of  the  observations  after  the 
giving  of  the  sodium-chloride  solution,  the  rate  in  each  case  being  materially 
lower  (usually  about  10  beats)  in  the  hour  or  two  after  the  injection  began 
than  in  the  preliminary  hour  previous  to  the  injection.  In  three  of  the 
experiments  with  the  mask  and  continuous  measurements,  this  fall  was  not 
very  marked  or  was  practically  absent,  although  there  were  variations  from 
period  to  period.  In  the  fourth  experiment  with  the  mask  (March  20), 
there  was  a  marked  fall,  but  the  indications  are  that  the  subject  had  quite 
recently  partaken  of  a  large  meal  which  was  sufficient  to  influence  the 
metabolism  at  the  beginning  of  the  experiment,  with  a  gradual  lessening  of 
this  effect  as  the  experiment  progressed. 

In  the  three  mouthpiece  experiments  with  subject  C  there  was  no  marked 
change  in  the  pulse-rate  in  the  first  (that  of  October  16),  while  in  the  other 
two  there  was  a  very  slight  fall  in  the  second  and  third  hours  after  the 
injection  began.  In  the  two  continuous  measurement  experiments  (with 
mask)  on  February  21  and  March  16  with  subject  C,  the  pulse-rate  fell 
markedly  when  the  subject  was  asleep  before  the  injection,  but  rose  when 
he  awoke.  The  pulse-rate  after  the  injection  was,  on  the  whole,  somewhat 
higher  than  the  rate  before  the  solution  was  given.  This  change  was,  in  all 
probability,  due  to  the  change  in  degree  of  wakefulness  rather  than  to  the 
solution  of  sodium  chloride. 

Subject  D  on  April  14  had  a  high  initial  pulse-rate  of  over  90  beats  per 
minute.  It  then  fell  during  a  period  of  sleep  and  subsequently  rose.  There 
was  no  general  change  in  the  course  of  the  pulse-rate  after  the  injection  took 
place. 

In  general,  in  this  series  there  was  a  tendency  when  the  subject  was  awake 
during  the  entire  evening  for  the  pulse-rate  to  fall  slightly  after  the  injection 
began,  but  when  he  slept  for  a  short  period  in  the  first  part  of  the  experiment 
and  awoke  before  the  injection  was  given,  the  pulse-rate  tended  to  remain 
unaltered  after  the  injection.  The  fall  in  pulse-rate  indicates  a  negative 
effect  in  respect  to  the  rectal  injection  of  sodium-chloride  solution  and  may 
be  taken  as  the  natural  course  of  the  pulse-rate  due  to  the  gradual  lowering 
of  physiological  processes  under  the  conditions  of  rest  in  the  early  hours  of 
evening.  During  measurements  of  the  respiratory  exchange  of  a  fasting 
man,  Benedict 1  found  the  pulse-rate  generally  slightly  higher  (1  to  6  beats) 
in  the  early  evening  (7h  00m  to  7h  45m  p.  m.)  than  for  the  same  condition  in 
the  morning  (8h  30m  to  9h  30m  a.  m.).  If  the  subject  has  a  short  period  of 
sleep  and  then  awakes,  he  has  recuperated  sufficiently  for  the  physiological 
processes  to  be  on  a  higher  plane  of  activity. 

Oxygen  Absorption. 

A  marked  variation  was  found  in  the  oxygen  absorption  of  subject  A  in 
the  mouthpiece  experiments,  with  a  fall  in  the  absorption  in  the  second  hour 
after  the  rectal  injection  began.  In  the  four  experiments  with  the  mask 
and  continuous  measurements,  there  was  likewise  considerable  variation. 


^Benedict:  Carnegie  Inst.  Wash.  Pub.  No.  203,  1915,  p.  114. 


94 


HUMAN  METABOLISM  WITH  ENEMATA. 


In  the  experiments  on  December  8  and  20,  the  oxygen  consumption  did  not 
change  materially  for  2  to  2\  hours  following  the  beginning  of  the  injection; 
on  December  8  there  was  a  decided  fall  at  the  end  of  the  third  hour.  On 
March  14,  the  oxygen  consumption  very  gradually  decreased  from  the 
beginning  of  the  experiment  until  the  end  of  the  observations,  with  a  total 
fall  after  the  beginning  of  the  injection  of  about  25  c.  c.  The  results  obtained 
on  March  20  are  doubtful,  because  apparently  the  whole  general  level  was 
somewhat  higher  than  usual,  and  the  decrease  was  marked  during  the  experi¬ 
ment,  this  being  presumably  due  to  the  preceding  diet. 

With  subject  C,  the  oxygen  absorption  in  the  three  experiments  with 
the  mouthpiece  likewise  varied,  but  the  variations  were  not  of  so  great  a 
magnitude  as  those  found  with  subject  A.  There  was  no  particular 
change  in  the  general  level  of  the  oxygen  consumption  which  may  be  con¬ 
sidered  a  result  of  the  rectal  injection  of  the  sodium-chloride  solution.  In 
the  mask  experiment  with  C  on  February  21  the  oxygen  consumption  was 
materially  lower  at  the  end  of  the  second  hour  after  the  injection  than  in 
the  first  hour  or  in  the  preliminary  period,  while  in  the  experiment  on  March 
16,  there  was  no  particular  change  after  the  injection  during  the  time  of  the 
measurements.  The  general  level  after  the  injection  was,  however,  slightly 
higher  than  in  the  preliminary  period,  but  this  can  be  explained  by  the  fact 
that  during  this  period  the  subject  was  asleep  for  a  short  time. 

In  the  one  experiment  with  subject  D  there  were  slight  variations  from 
period  to  period,  but  these  were  not  so  marked  as  with  the  preceding  sub¬ 
jects,  and  the  oxygen  consumption  did  not  change  materially  during  the 
course  of  the  observations. 

In  general,  there  was  in  this  series  of  experiments  a  tendency  for  the  oxygen 
absorption  to  fall  off  during  the  several  hours  of  the  evening  experiment, 
more  particularly  in  the  latter  part  of  the  observations,  or  the  oxygen  con¬ 
sumption  remained  unaltered,  but  there  was  no  general  change  in  this  factor 
which  may  be  ascribed  logically  to  the  rectal  injection  of  the  sodium-chloride 
solution. 


Respiratory  Quotient. 

Theoretically,  the  injection  of  a  solution  of  sodium  chloride  into  the 
rectum  should  produce  no  alteration  in  the  course  of  the  respiratory  quotient, 
and  it  should  continue  at  the  level  usual  in  a  series  of  periods  5  to  10  hours 
after  a  light  meal.  From  past  experience  in  observations  of  the  respiratory 
quotient  in  half-hour  periods,  it  would  be  expected  that  normally  there  would 
be  slight,  if  any,  change  in  the  course  of  2  to  4  hours  with  successive  measure¬ 
ments. 

A  notable  feature  in  the  mouthpiece  experiments  with  subject  A  is  the 
extraordinarily  wide  variation  in  the  respiratory  quotient  from  period  to 
period  which  occurred  both  in  the  preliminary  measurements  and  in  the 
periods  subsequent  to  the  injection  of  the  solution.  Part  of  this  variation 
was  undoubtedly  due  to  varying  conditions  of  drowsiness,  as  well  as  to  the 
natural  inconstancy  of  the  subject  himself.  No  effect  of  the  injection  upon 
the  course  of  the  quotient  was  apparent  in  three  of  the  four  experiments. 
In  the  remaining  experiment  there  was  a  tendency  for  the  quotient  to  fall 
in  the  second  hour  after  injection. 

The  four  experiments  with  subject  A  in  which  the  measurements  were 


RESPIRATORY  EXCHANGE  WITH  SODIUM  CHLORIDE.  95 


made  continuously  also  exhibit  variability  in  the  respiratory  quotient  from 
period  to  period.  Accordingly,  it  must  be  taken  for  granted  that  the  varia¬ 
tion  in  the  mouthpiece  experiments  was  not  due  to  the  pumping-out  of  the 
carbon  dioxide  and  then  a  subsequent  recovery  in  the  interval  when  there 
were  no  measurements,  but  that  it  was  a  true  variability  and  occurred  re¬ 
gardless  of  whether  the  measurements  were  made  continuously  or  at  intervals. 
In  spite  of  this  variability,  however,  the  four  continuous  measurements  in 
the  experiments  with  the  mask  indicated  no  general  alteration  in  the  level 
of  the  respiratory  quotient  subsequent  to  the  injection  of  the  sodium-chloride 
solution.  Consequently,  the  conclusion  may  be  drawn  that  the  injection 
of  a  sodium-chloride  solution  with  subject  A  did  not  per  se  produce  a  change 
in  the  respiratory  quotient,  and  such  changes  as  occurred  were  those  which 
would  normally  take  place  in  the  course  of  several  hours. 

With  subject  C  there  were  five  experiments,  in  three  of  which  the  mouth¬ 
piece  was  used  and  the  measurements  were  made  at  intervals.  While  the 
variability  in  the  respiratory  quotient  from  period  to  period  was  not  quite 
so  great  as  with  subject  A,  the  group  of  experiments  as  a  whole  indicated  a 
slight  lowering  of  the  respiratory  quotient  during  the  several  hours  of  the 
experiment;  that  is,  in  the  second  or  third  hour  after  the  rectal  injection, 
the  quotient  was  lower  than  in  the  hour  preceding  the  injection. 

The  two  experiments  with  C  in  which  continuous  measurements  were 
made  are  complicated  by  a  period  of  sleep  of  nearly  30  minutes  during  the 
preliminary  observations,  which  occasioned  a  marked  depression  in  the  re¬ 
spiratory  quotient.  When  the  subject  awoke,  the  quotient  rose  immediately, 
but  after  the  injection  was  given  it  did  not  undergo  marked  alteration  dur¬ 
ing  a  period  of  2  hours.  We  have,  therefore,  two  different  groups  of 
evidence  regarding  the  effect  of  the  injection  of  a  sodium-chloride  solution 
upon  the  respiratory  quotient.  In  the  first  group  there  was  a  slight  fall 
which  was,  in  all  probability,  due  to  a  lowering  of  the  metabolism  and  a 
tendency  towards  fatigue  and  drowsiness  at  the  end  of  the  period;  in  the 
other,  with  sleep  in  the  preliminary  periods,  the  subsequent  measurements 
showed  no  alteration  in  the  quotient. 

In  the  one  experiment  with  subject  D,  continuous  measurements  were 
made.  A  period  of  sleep  during  the  preliminary  hour  resulted  in  a  marked 
depression  of  the  respiratory  quotient  with  a  subsequent  rise  to  above  the 
initial  level  after  the  injection  was  given  and  practical  constancy  thereafter 
for  a  period  of  nearly  2j  hours. 

The  course  of  the  respiratory  quotient  as  measured  in  these  experiments 
during  the  evening  hours  has  possibly  a  tendency  towards  a  slight  fall, 
particularly  after  a  period  of  2  or  3  hours;  this  fall  was  not  due  to  the  injec¬ 
tion  of  the  sodium-chloride  solution,  but  rather  to  a  natural  drowsiness  or 
fatigue  occurring  at  the  end  of  the  day.  In  experiments  in  which  the  sub¬ 
ject  was  asleep  for  most  of  the  time,  or  when  there  was  a  period  of  sleep 
followed  by  wakefulness,  the  quotient  was  not  lowered.  It  is  evident  that 
the  conditions  under  which  these  experiments  were  carried  out  were  not 
ideal  for  the  study  of  such  a  fine  point  as  the  slight  alterations  in  the  respira¬ 
tory  quotient.  Subjects  should  be  chosen  who  have  low  deviations  in 
results  and  who  are  able  to  maintain  a  uniform  degree  of  wakefulness.  It 
would  be  better,  also,  to  have  the  experiments  in  the  morning,  rather  than 
in  the  evening. 


96 


HUMAN  METABOLISM  WITH  ENEMATA. 


At  the  time  this  research  was  begun,  the  afternoon  hours  were  chosen  for 
carrying  out  the  experiments,  with  no  thought  that  the  time  of  day  might 
affect  the  constancy  of  the  metabolism,  and  it  was  believed  that  with  trained 
subjects  it  would  be  possible  to  secure  the  same  results  as  would  be  secured  if 
the  observations  were  made  in  the  morning  hours.  After  the  experiments 
had  been  completed,  it  was  realized  that  there  was  not  the  same  degree  of 
uniformity  at  this  period  of  the  day  as  in  the  early  morning  hours.  One  re¬ 
sult  of  the  observations  as  a  whole  has  been,  therefore,  to  show  that,  in  all 
likelihood,  when  the  individual  is  somewhat  fatigued  or  has  reached  the  end 
of  a  day’s  work,  the  metabolism  and  the  physiological  functions  are  not  so 
stable  as  after  an  ordinary  night’s  rest.  This  is  a  subject  which  needs  further 
investigation. 


GENERAL  CONCLUSIONS  AND  DISCUSSION  OF  COMPOSITE  CHART. 

These  experiments  with  rectal  injection  of  sodium-chloride  solution  may  be 
looked  upon  as  negative  in  their  results  so  far  as  any  effect  of  the  solution 
itself  or  the  method  of  its  administration  are  concerned,  and  therefore  they 
may  be  taken  as  controls  to  indicate  the  general  trend  of  the  pulse-rate,  oxy¬ 
gen  absorption,  and  respiratory  quotient  of  these  three  subjects.  While 


Fig.  19. — Chart  showing  composite  results 
for  measurements  of  respiratory  quo¬ 
tient,  oxygen  absorption,  and  pulse- 
rate  in  14  experiments  with  rectal  injec¬ 
tion  of  a  0.6  per  cent  solution  of  sodium 
chloride.  (Mouthpiece  or  mask.) 


COMPOSITE  CHART  RECTAL  INJECTION  OF  0.6  PER  CENT 
SODIUM  CHLORIDE  SOLUTION 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


they  are  not  “basal”,  they  will,  however,  serve  as  a  basis  of  comparison 
for  the  effect  of  rectal  injection  of  alcohol  in  varying  concentrations  and 
amounts,  and  of  dextrose  and  levulose  solutions.  The  comparison  will  not 
be  made  by  subtracting  these  values  from  the  values  obtained  in  the  other 
experiments,  but  by  comparing  the  trend  in  the  alcohol,  dextrose,  and  levu¬ 
lose  experiments  with  the  trend  in  the  experiments  with  the  sodium-chloride 
solution,  and  by  comparing  the  several  portions  of  the  experiments  with  each 
other  and  with  the  values  obtained  previous  to  the  rectal  injection. 

A  composite  chart  has  been  made  of  all  the  sodium-chloride  experiments  in 
which  either  the  mouthpiece  or  the  mask  was  used  and  is  given  in  figure  19. 
This  has  been  prepared  by  first  making  a  tracing  of  all  the  charts  on  a  sheet  of 
transparent  paper,  and  then  the  composite  was  drawn  freehand  as  an  esti¬ 
mated  average  of  all  the  experiments. 

Pulse-rate . — The  average  pulse-rate  is  shown  in  the  chart  for  40  minutes 
before  injection  and  for  3  hours  after  injection.  The  pulse-rate  before  in¬ 
jection  had  a  composite  average  of  slightly  over  66  beats  per  minute.  This 
fell  slightly  during  the  first  hour  after  injection.  During  the  second  and  third 
hours  there  was  a  material  depression  in  the  pulse-rate  to  an  average  of  60 
beats  per  minute  at  the  end  of  the  third  hour.  The  general  course  of  the 


RESPIRATORY  EXCHANGE  WITH  SODIUM  CHLORIDE.  97 


pulse-rate  was  therefore  gradually  downward  throughout  the  entire  period  of 
observation. 

Oxygen  absorption. — The  oxygen  absorption  was  practically  constant  at  a 
level  of  about  235  c.  c.  per  minute  before  injection.  After  injection,  the 
average  rose  slightly  but  began  to  fall  in  about  hours  after  injection. 
The  final  average  at  the  end  of  3  hours  approximated  213  c.  c.  per  minute, 
which  is  considerably  below  the  initial  level  before  the  injection.  For  much 
of  its  course  the  oxygen  curve  practically  parallels  the  curve  for  the  pulse- 
rate.  This  finding  is  of  importance  in  connection  with  the  general  question 
of  the  parallelism  between  the  pulse-rate  and  the  oxygen  absorption  which 
has  been  brought  out  in  many  publications  from  the  Nutrition  Laboratory. 

Respiratory  quotient. — The  respiratory  quotient  is  of  importance  as  an  indi¬ 
cation  of  the  degree  of  utilization  of  the  material  injected.  Theoretically, 
the  injection  of  a  sodium-chloride  solution  should  produce  no  change  in  the 
respiratory  quotient.  The  average  respiratory  quotient  in  this  series  of  ex¬ 
periments  was  practically  unchanged  throughout  the  entire  experimental 
period  of  3  hours  and  40  minutes.  This  conclusion  differs  slightly  from  that 
drawn  on  page  95,  which  was  based  more  particularly  on  selected  experiments 
rather  than  on  the  group  as  a  whole.  It  must  be  noted  that  this  composite 
chart  includes  all  of  the  experiments,  regardless  of  whether  the  subject  was 
asleep  a  portion  or  all  of  the  time,  or  whether  he  was  asleep  in  the  early  part 
of  the  observations  and  awake  later.  In  general,  the  average  of  all  the  re¬ 
spiratory  quotients  during  the  experimental  periods  does  not  change. 

Sodium-Chloride  Experiments  with  the  Clinical  Respiration 

Chamber. 

In  the  winter  of  1916-17,  a  few  control  experiments  were  carried  out  with 
subject  A  which  continued  for  the  entire  night.  In  these  the  clinical  respira¬ 
tion  chamber  1  was  used  for  determining  the  respiratory  exchange.  The 
general  procedure  was  practically  the  same  as  that  used  with  the  breathing 
appliance  and  gasometer  method.  The  subject  usually  had  a  substantial 
meal  at  noon,  but  no  food  afterwards.  In  all  but  the  first  experiment,  tests 
connected  with  another  research  were  made  with  him  in  the  early  part  of  the 
evening.2  Before  the  measurement  of  the  respiratory  exchange  he  took  an 
enema  to  cleanse  the  rectum  and  the  large  intestine,  and  after  removing  all 
clothing  but  his  underwear,  he  lay  down  on  a  woven-wire  bed-spring  in  the 
chamber.  The  catheter  for  the  introduction  of  the  solution  was  then  in¬ 
serted.  This  catheter  was  connected  to  the  feeding  reservoir  by  means  of  a 
capillary  U-tube  placed  in  the  water-seal  of  the  respiration  chamber;  it  was 
thus  possible  to  introduce  the  solution  at  any  time  after  the  cover  of  the 
apparatus  had  been  put  in  place.  Two  pneumographs  and  a  stethoscope 
were  attached  to  the  subject  as  in  the  breathing-appliance  experiments.  In 
the  last  three  experiments  in  the  series,  standard  electro-cardiograms  were 
secured,  and  for  this  purpose  cheese-cloth  electrodes,  saturated  in  a  solution 
of  sodium  chloride,  were  wrapped  around  his  left  ankle  and  both  wrists  and 
connected  to  a  string  galvanometer.3  After  the  subject  had  been  covered 


1  Benedict  and  Tompkins:  Boston  Med.  and  Surg.  Journ.,  1916,  174,  pp.  857,  898,  and  939. 

J  Miles:  Carnegie  Inst.  Wash.  Pub.  No.  333,  1924,  pp.  111-124. 

*  For  a  detailed  description  of  the  electrodes  and  the  standard  electro-cardiograms  obtained,  see 
Miles:  Carnegie  Inst.  Wash.  Pub.  No.  333,  1924,  pp.  119-124. 


/ 


98 


HUMAN  METABOLISM  WITH  ENEMATA. 


with  two  blankets,  he  was  ready  for  the  observations  of  the  respiratory  ex¬ 
change.  In  spite  of  the  various  attachments  and  the  confinement  of  the 
chamber,  the  man  was  able  to  turn  from  side  to  side  and  to  sleep  the  greater 
part  of  the  night. 

After  the  preliminary  preparations  had  been  completed,  the  cover  of  the 
apparatus  was  put  in  place,  the  circulation  of  the  air  was  started,  and  obser¬ 
vations  were  begun  as  soon  as  equilibrium  conditions  were  obtained  inside 
the  chamber.  Usually  three  periods  of  approximately  one-half  hour  each 
were  completed  before  the  introduction  of  the  solution  began.  The  experi¬ 
ment  was  then  continued  throughout  the  night  with  periods  of  about  equal 
length.  Some  of  the  clinical-chamber  experiments  were  preceded  and  fol¬ 
lowed  by  a  few  periods  with  the  breathing-appliance  (mask)  apparatus. 

These  observations  with  the  clinical  respiration  chamber  are  discussed  here 
in  much  the  same  manner  as  those  made  by  the  breathing-appliance  and 
gasometer  method.  There  were  four  experiments  in  all,  one  with  distilled 
water,  two  with  a  0.6  per  cent  solution  of  sodium  chloride,  and  one  with  no 
rectal  injection.  A  list  of  the  experiments  is  given  in  table  22,  and  the  results 


Table  22. — Control  experiments  with  subject  A  in  a  clinical  respiration  chamber  with  rectal 

injection. 


Date. 

Solution  injected. 

Duration 

of 

injection. 

Periods  before 
injection. 

Periods  after 
injection. 

Volume. 

Weight 

NaCl. 

No. 

Time 

covered. 

No. 

Time 

covered. 

1917. 

c.  c. 

grams. 

min. 

h.  min. 

h.  min. 

Jan.  13 — 14  .  . 

500 

0 

30 

3 

1  41 

9 

6  1 

Feb.  9-10  .  . 

500 

3.0 

3 

1  34 

10 

5  28 

Mar.  16-17  . . 

0 

0 

#  # 

0 

0  0 

14 

7  1 

Apr.  2—  3  . . 

500 

3.0 

76 

2 

1  26 

8 

6  2 

are  presented  in  the  form  of  curves  in  figures  20  to  23.  The  chamber  res¬ 
piration  experiments  were  conducted  primarily  as  controls  for  the  experi¬ 
ments  with  subject  A,  in  which  a  7.5  per  cent  alcohol  solution  was  injected, 
and  the  measurements  were  continued  throughout  the  night.  The  mask 
and  gasometer  experiments  at  the  beginning  or  end  of  the  chamber  observa¬ 
tions  were  made  more  especially  to  secure  information  as  to  conditions  at  the 
beginning  and  end  of  the  main  experiment,  and  not  primarily  for  the  study 
of  differences  in  the  metabolism  and  pulse-rate  with  the  subject  asleep  and 
awake.  And  yet  they  do  contribute  to  this  problem,  as  in  many  cases  the 
subject  was  awake  in  the  morning. 

Pulse-Rate. 

In  three  out  of  four  of  the  chamber  respiration  experiments,  the  pulse- 
rate  maintained  a  fairly  constant  level  from  beginning  to  end.  On  March 
16-17  there  was  a  marked  fall  at  the  very  end,  while  in  the  experiment  on 
April  2-3  there  was  a  difference  of  5  beats  between  the  first  and  second  periods 
before  the  injection  took  place  and  when  the  subject  was  in  the  respiration 
chamber.  In  the  experiment  on  January  13-14,  for  some  unknown  reason  the 


RESPIRATORY  EXCHANGE  WITH  SODIUM  CHLORIDE. 


99 


pulse-rate  was  somewhat  higher  in  the  last  2\  hours  of  the  experiment  than  in 
the  previous  periods.  The  highest  pulse-rate,  however,  was  only  65  beats, 
which,  for  this  subject,  is  not  a  very  high  rate.  The  experiments  as  a  whole 
do  not  indicate  any  particular  period  of  time  when  there  was  an  absolute 


SUBJECT  A.  JAN.  13-14.  1917 

500  c.c.  DISTILLED  WATER  CHAMBER  RESPIRATION  APPARATUS 


0.90 

0.85 

080 

200 

175 

150 

60 

55 


RESPIRATORY  QUOTIENT 


02  PER  MINUTE,  c.  c. 


C02  PER  MINUTE,  c.c. 


PULSE  PER  MINUTE 

r 


'awake 

asleep! 


I 


JL 


0  1  2  3  4  5  6 

HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


10 


1 1 


12 


Fig.  20. — Respiratory  quotient,  oxygen  absorption,  carbon-dioxide  elimination,  and  pulse-rate 
of  subject  A,  January  13-14,  1917,  before  and  after  rectal  injection  of  500  c.  c.  of  distilled 
water.  (Chamber  respiration  apparatus.) 

The  horizontal  line  at  the  bottom  of  this  and  subsequent  charts  gives  a  record  of  sleep,  the 
solid  portions  indicating  when  the  subject  was  asleep,  and  the  broken  portions  when  he  was 
awake. 


SUBJECT  A.  FEB.  9-10.  1917 

500  c. c.NaCI  SOLUTION  CHAMBER  RESPIRATION  APPARATUS 


0.90 

0.85 

0.80 

225 

200 

175 

150 

70 

65 

60 


RESPIRATORY  QUOTIENT 


,02  PER  MINUTE,  c.c 


C02  PER  MINUTE,  c 


c. 


AWAKE 


PULSE  PER  MINUTE 


T 


ASLEEP 


JL 


X 


X 


0  1  2  3  4  5  6 

HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


10  11  12 


Fig.  21. — Respiratory  quotient,  oxygen  absorption,  carbon-dioxide  elimination,  and  pulse-rate 
of  subject  A,  February  9-10,  1917,  before  and  after  rectal  injection  of  500  c.  c.  of  a  0.6  per 
cent  solution  of  sodium  chloride.  (Chamber  respiration  apparatus,  followed  by  observa¬ 
tions  with  mask  and  gasometer  apparatus.) 


minimum  for  the  night.  In  the  three  cases  in  which  measurements  were 
made  with  a  mask  and  gasometer  after  the  experiment  with  the  chamber  was 
concluded,  the  pulse-rate  was  materially  higher,  but  at  this  time  the  subject 
was  awake  during  practically  the  entire  observation. 


100 


HUMAN  METABOLISM  WITH  ENEMATA. 


The  general  level  of  the  pulse-rate  for  the  first  experiment  was  slightly 
lower  than  the  subject’s  basal  pulse-rate  (64  beats  per  minute),  while  that 
for  the  experiment  of  February  9-10  was  very  nearly  basal.  The  level  on 
March  16-17  was  about  5  beats  higher  than  the  basal  rate,  while  the  pulse- 


SUBJECT  A  MAR  16-17  1917  CHAMBER  RESPIRATION  APPARATUS 


Fig.  22. — Respiratory  quotient,  oxygen  absorption,  carbon-dioxide  elimination,  and  pulse-rate  of 
subject  A,  March  16-17,  1917,  with  no  rectal  injection.  (Chamber  respiration  apparatus, 
preceded  and  followed  by  observations  with  mask  and  gasometer  apparatus.) 


SUBJECT  A  APR  2-3  1917 

500  c.c  NaCi  SOLUTION  CHAMBER  RESPIRATION  APPARATUS 

- - , - p- - » - 1 - 1 - - 


:os5 

080 

0.75 

,0.70 

225 

200 

175 

J50 

80 

75 

70 

RES 

^IRAT 

ORY 

QUO' 

FIEN1 

r 

SK 

lr 

M> 

\SK 

j 

MA 

R.( 

RQ 

1  - 1 

h 

J 

p-l 

c 

02F 

>ER  M 

INUT 

E.cc 

1 

0?  1 _ 

l 

|— 

n 

r—  L 

co2 

=>ER  t 

■1INU" 

FE  c.c 

J 

C02  r- 

i 

.PUL 

n 

bh 

ra 

PULSE  - 

PUL 

.SE  P 

ER  N 

1INU" 

rE 

AY 

/AKE 

•  •  ■  • 

ASLEEP— 

i  i 

1 

1  1 

■  I  I  I  I  I  .  I  I  _ I  1  ""  I _ I _ I _ 1 _ 

0  I  2  3  4  5  6  7  8  9  10  l_l  12  13 

HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


Fig.  23. — Respiratory  quotient,  oxygen  absorption,  carbon-dioxide  elimination,  and  pulse-rate  of 
subject  A,  April  2-3, 1917,  with  rectal  injection  of  500  c.  c.  of  a  0.6  per  cent  solution  of  sodium 
chloride.  (Chamber  respiration  apparatus,  preceded  and  followed  by  observations  with  mask 
and  gasometer  apparatus.) 

level  of  75  beats  on  April  2-3  was  distinctly  higher  (11  beats)  than  the  basal 
pulse-rate. 

As  the  subject  was  awake  in  the  three  morning  experiments  with  the  mask 
and  gasometer  and  asleep  in  the  chamber  experiments  just  previous  to  these, 


RESPIRATORY  EXCHANGE  WITH  SODIUM  CHLORIDE.  101 


they  give  information  as  to  the  change  in  pulse-rate  which  took  place  with 
this  change  from  asleep  to  awake.  On  February  10  the  increase  in  rate  per 
minute  was  7  beats  (from  64  to  71  beats);  on  March  17  the  increase  was  11 
beats  (from  63  to  74  beats) ;  on  April  3  the  increase  was  7  beats  (from  79  to  86 
beats).  It  is  seen  from  these  results  that  this  subject,  when  awake  imme¬ 
diately  after  a  night’s  sleep,  showed  a  marked  increase  in  the  heart-rate  of  7 
to  11  beats. 

Carbon-Dioxide  Elimination. 

The  carbon-dioxide  elimination  is  included  in  the  charts  for  this  series  for 
the  reason  that  with  this  apparatus  its  changes  may  be  measured  more 
accurately  than  those  of  the  oxygen  absorption,  and  it  gives  a  better  indica¬ 
tion  of  the  real  trend  of  the  total  metabolism,  as  well  as  of  the  respiratory 
quotient,  provided  the  oxygen  absorption  does  not  alter.  In  three  of  the 
four  experiments  the  carbon-dioxide  elimination  had  a  slight  tendency  to  rise. 
This  is  most  marked  in  the  experiments  of  January  13-14  and  February  9-10, 
while  somewhat  the  same  tendency  is  apparent  in  the  chart  for  the  experi¬ 
ment  of  March  16-17.  For  some  unexplainable  reason,  the  carbon-dioxide 
elimination  in  the  experiment  of  March  16-17  shows  a  type  of  alternation 
which  would  not  be  expected  under  these  conditions.  This  tendency  for  the 
carbon-dioxide  elimination  to  rise  confirms  the  same  tendency  found  with 
the  respiratory  quotient.  The  values  for  the  carbon  dioxide  measured  in 
short  periods  after  the  chamber  experiment  was  over  are  always  somewhat 
higher  than  those  determined  with  the  chamber  apparatus,  but  again  it  must 
be  recalled  that  the  subject  was  usually  awake  in  these  periods,  while  in  the 
chamber  he  was  asleep. 

From  the  values  given  in  the  charts,  a  comparison  may  be  made  of  the 
carbon-dioxide  production  with  the  subject  asleep  and  awake.  The  in¬ 
creases  are:  February  10,  18  c.  c.  (from  172  to  190  c.  c.);  March  17,  21  c.  c. 
(from  174  to  195  c.  c.);  and  April  3,  20  c.  c.  (from  175  to  195  c.  c.).  As  the 
respiratory  quotients  are  practically  the  same  for  both  conditions  in  the 
morning,  these  increases  show  the  metabolic  increase  in  the  change  from 
asleep  to  awake,  i.  e.,  about  11  per  cent. 

Oxygen  Absorption. 

The  oxygen  absorption  is  liable  to  show  variable  figures  in  experiments 
with  the  clinical  respiration  chamber  because  of  the  difficulty  in  measuring 
the  average  temperature  at  the  end  of  each  period.  In  two  of  these  experi¬ 
ments,  however  (January  13-14  and  February  9-10),  there  is  a  general 
tendency  toward  a  slight  rise  in  this  factor,  the  values  on  February  9-10 
being  the  most  consistent  of  any  in  the  four  experiments.  The  other  two 
experiments  exhibit  no  tendency  toward  a  change  in  either  direction.  As 
with  the  carbon-dioxide  elimination,  the  values  obtained  in  the  morning  with 
the  gasometer  and  mask  are  materially  higher  than  those  obtained  during  the 
night  with  the  chamber  apparatus.  The  increases  in  the  oxygen  consump¬ 
tion  when  the  subject  awoke  in  the  morning  were  as  follows:  February  10, 
23  c.  c.  (from  201  to  224  c.  c.);  March  17,  19  c.  c.  (208  to  227  c.  c.);  and  April 
3,  30  c.  c.  (215  to  245  c.  c.).  The  average  increase  was  24  c.  c.  per  minute, 
i.  e.,  slightly  over  11  per  cent.  The  increase  in  the  oxygen  consumption  of 
this  subject  in  the  morning  change  from  asleep  to  awake  was  thus  of  the  same 
order  as  the  change  in  the  carbon-dioxide  production. 


102 


HUMAN  METABOLISM  WITH  ENEMATA. 


Respiratory  Quotient. 

The  respiratory  quotient  did  not  change  very  materially  in  one  direction 
or  the  other,  although  it  varied  from  period  to  period.  These  variations, 
however,  probably  do  not  represent  true  changes  in  the  respiratory  quotient, 
but  rather  indicate  the  difficulty  of  measuring  quotients  with  the  chamber 
apparatus  in  short  periods.  The  least  variation  is  found  in  the  experiment 
on  February  9-10,  in  which  slight  or  no  change  occurred  in  the  respiratory 
quotient  from  the  beginning  of  the  experiment  until  the  end.  A  measure¬ 
ment  with  the  gasometer  and  mask  combination  is  in  accord  with  the 
quotient  obtained  in  the  morning.  In  three  of  the  experiments  there  was  a 
slight  tendency  for  the  quotient  to  rise  during  the  night.  This  is  shown  most 
markedly  in  the  experiment  of  March  16-17,  and  the  end-quotients  confirm 
those  obtained  with  the  gasometer  and  mask.  The  same  change  may  be 
seen  in  the  experiment  of  April  2-3,  though  not  to  so  marked  a  degree,  and 
there  is  a  slight  tendency  towards  a  rise  in  the  experiment  of  January  13-14. 

A  change  in  the  quotient  between  the  evening  and  morning  has  already 
been  found  in  a  series  of  experiments  with  a  fasting  man1  whose  metabolism 
was  measured  by  the  universal  respiration  apparatus  in  the  evening  before 
he  went  into  the  chamber  of  the  respiration  calorimeter,  in  which  he  spent 
the  night,  and  again  in  the  morning  immediately  after  he  left  the  chamber. 
In  every  case,  the  morning  respiratory  quotient  of  this  fasting  man  was 
slightly  higher  (0.01  to  0.05)  than  the  evening  respiratory  quotient  obtained 
under  the  same  conditions  of  measurement.  The  interpretation  given  was 
that  this  lowering  of  quotient  in  the  evening  experiments  might  be  taken  as 
an  indication  either  that  there  was  a  formation  from  fat  of  carbohydrate 
which  in  the  morning  was  burned,  or  that  there  was  a  greater  formation  of 
/3-oxybutyric  acid  in  the  evening  than  in  the  morning.  Benedict  did  not 
consider  it  justifiable  to  lay  much  stress  on  the  differences  in  quotient,  but  it 
is  evident  from  the  experiments  with  subject  A  that  the  differences  with 
the  fasting  man  were  really  of  significance 

It  is  evident  from  the  experiments  reported  in  this  monograph  that  the 
process,  whatever  it  is,  is  a  very  gradual  one  and  that  the  increase  is  not 
large.  One  may  suppose  that  at  the  end  of  the  waking  period  the  readily 
available  supply  of  high  quotient  material  (carbohydrate)  has  reached  its 
minimum  and  that  the  condition  of  minimum  activity  during  sleep  brings 
about  a  condition  in  which  this  material  can  be  formed  more  rapidly  than  it  is 
utilized.  As  a  result,  there  is  a  gradual  increase  in  availability  and  in  conse¬ 
quence  a  greater  utilization  of  the  high  quotient  material  in  metabolism. 
Whether  it  is  carbohydrate  formation  from  fat,  a  gradual  decrease  in  par¬ 
tially  oxidized  products,  or  a  gradually  increasing  availability  of  the  carbo¬ 
hydrate  portion  of  protein  can  not  be  stated  from  these  experiments. 

Experiments  are  needed  to  determine  more  exactly  the  rate  and  amount  of 
the  increase  in  the  respiratory  quotient  during  a  night’s  sleep  and  the  nutri¬ 
tive  conditions  which  govern  it.  From  the  experiments  by  Benedict  on  the 
fasting  man  and  the  series  here  reported,  it  is  evident  that  the  increase  in  the 
respiratory  quotient  as  the  result  of  long  periods  of  sleep  is  a  real  change  in 
metabolism. 


1  Benedict:  Carnegie  Inst.  Wash.  Pub.  No.  203,  1915,  p.  334,  table  46;  also  p.  338. 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  103 


GENERAL  CONCLUSIONS  REGARDING  EXPERIMENTS  WITH  CLINICAL 

RESPIRATION  CHAMBER. 

In  general,  it  may  be  said  that  in  the  control  experiments  made  during  the 
night,  the  pulse-rate  remained  practically  unaltered,  except  as  it  was  affected 
by  variations  in  wakefulness;  that  the  carbon-dioxide  elimination  rose  slight¬ 
ly;  that  the  oxygen  absorption  rose  very  slightly  or  remained  unchanged  as 
the  night  progressed ;  and  that  the  respiratory  quotient  had  but  a  slight  tend¬ 
ency  to  alter,  and  that  this  tendency  was  in  the  upward  direction.  The 
changes,  therefore,  are  such  as  would  presumably  occur  in  normal  night  ex¬ 
periments  and  may  be  looked  upon  as  contributions  to  the  normal  metabo¬ 
lism  during  sleep.  In  discussing  the  course  of  the  metabolism  and  pulse-rate 
in  the  night  experiments  with  the  chamber  apparatus  in  which  a  7.5  per  cent 
alcohol  solution  was  given,  these  chamber  experiments  in  the  sodium-chloride 
series  will  be  used  as  a  basis  of  comparison.  (See  p.  120.)  As  the  experi¬ 
ments  in  this  series  were  few  in  number  and  dissimilar  as  to  character  of 
injection,  no  composite  chart  has  been  made  for  them. 

RESPIRATORY  EXCHANGE  WITH  RECTAL  INJECTION  OF 

ALCOHOL  SOLUTIONS. 

As  has  previously  been  brought  out,  this  investigation  was  begun  primarily 
as  a  study  upon  the  effect  of  the  rectal  injection  of  alcohol  solutions,  the 
sodium-chloride  experiments  being  made  simply  as  controls.  The  method  of 
conducting  the  alcohol  experiments  was  the  same  as  for  the  control  experi¬ 
ments.  The  concentrations  of  the  ethyl  alcohol  in  the  solutions  used  were 
5,  7.5,  and  10  per  cent  by  weight  in  distilled  water.  The  solution  was  made 
up  from  a  concentrated  alcohol  whose  strength  had  been  estimated  from  den¬ 
sity  values  determined  with  a  Squibb  50-c.  c.  pyknometer.  In  the  discussion 
of  the  results,  the  experiments  are  grouped,  first,  according  to  the  percentage 
of  alcohol  in  the  solution;  second,  according  to  the  volume  of  the  solution 
injected;  and  third,  according  to  subjects. 

Experiments  with  a  5  per  cent  Alcohol  Solution. 

The  first  group  of  observations  with  alcohol  injection  was  made  with  a  5 
per  cent  solution  of  alcohol.  Table  23  shows  the  number  and  character  of 
the  experiments  grouped  according  to  volume  and  subject.  These  experi¬ 
ments  were  carried  out  with  the  same  individuals  and  in  the  same  manner  and 
under  the  same  conditions,  except  for  the  solution  injected,  as  the  experi¬ 
ments  with  the  sodium-chloride  solution,  i.  e.,  they  were  usually  late  in  the 
afternoon,  the  last  food  taken  by  the  subject  being  in  the  morning.  In  two 
of  the  experiments  the  subject  was  post-absorptive,  namely,  those  with  A  on 
October  12,  and  with  C  on  October  24.  In  the  other  mouthpiece  experi¬ 
ments,  the  last  food  was  taken  not  later  than  lh  30m  p.  m.,  and  usually  before 
9  a.  m.  The  experiments  generally  began  about  5h  30m  p.  m. 

The  volume  injected  varied  from  220  c.  c.  to  1,020  c.  c.  Using  round 
numbers,  there  were  2  experiments  with  200  c.  c.,  6  with  300  c.  c.,  4  with  400 
c.  c.,  3  with  500  c.  c.,  and  1  with  1,020  c.  c.  The  time  of  injection  was  not 
recorded  in  all  of  the  experiments,  but  such  records  as  are  available  vary  from 
1  to  68  minutes,  except  in  the  experiment  of  April  17,  when  it  was  270 
minutes.  In  all  but  one  experiment,  observations  preceded  the  giving  of  the 
alcohol,  the  number  of  periods  before  injection  ranging  from  1  to  8,  and  the 


104 


HUMAN  METABOLISM  WITH  ENEMATA. 


length  of  period  from  4  to  15  minutes.  The  total  period  of  time  covered 
ranged  from  4  minutes  to  1  hour  and  14  minutes.  The  number  of  periods 
after  injection  varied  from  9  to  26,  and  the  time  covered  from  1  hour  and  58 
minutes  to  6  hours  and  1 1  minutes.  In  the  discussion,  the  observations  be¬ 
fore  the  injection  are  first  considered  and  then  the  data  obtained  during  and 
subsequent  to  the  injection.  In  discussing  the  latter,  the  experiments  are 
grouped  according  to  the  volume  of  the  injection,  i.  e.,  approximately  200, 
300,  400,  and  500  to  1,000  c.  c.,  with  a  general  summary  of  the  effect  of 
the  alcohol.  The  results  of  the  observations  are  given  graphically  in  figures 
24  to  39. 


Table  23. — Statistics  of  respiratory  exchange  observations  before  and  after  the  injection  by 

rectum  of  a  5  per  cent  alcohol  solution. 


Subject. 

Date." 

Alcohol 

injected. 

Duration 

of 

injection. 

Periods  before 
injection. 

Periods  after 
injection. 

Volume  of 
solution. 

Weight  of 
alcohol. 

No. 

Time 

covered. 

No. 

Time 

covered. 

1915. 

c.  c. 

gm. 

min. 

h. 

min. 

h. 

min. 

A 

Oct.  5 

220 

11 

1 

3 

0 

40 

11 

3 

28 

Oct.  8 

220 

11 

10 

3 

0 

36 

11 

3 

19 

Oct.  12b 

320 

16 

11 

3 

0 

36 

17 

5 

6 

Oct.  27 

300 

15 

,  , 

5 

1 

0 

9 

2 

49 

Nov.  10 

320 

16 

25 

3 

0 

32 

15 

3 

18 

C 

Oct.  24b 

325 

16.3 

5 

5 

1 

3 

12 

2 

37 

Oct.  29 

320 

16 

3 

1 

0 

4 

15 

3 

46 

Nov.  8 

320 

16 

.  , 

4 

0 

35 

15 

3 

24 

A 

Nov.  18 

400 

20 

11 

4 

0 

54 

10 

1 

58 

Nov.  24 

420 

21 

13 

8 

1 

14 

17 

2 

30 

Dec.  2 

420 

21 

.  , 

7 

1 

6 

21 

3 

11 

C 

Nov.  29 

420 

21 

33 

6 

1 

1 

18 

2 

28 

1916. 

A 

Apr.  3 

510 

25.5 

68 

0 

0 

0 

23 

3 

59 

D 

Feb.  18 

520 

26 

33 

6 

1 

0 

20 

3 

20 

Feb.  25 

510 

25.5 

47 

7 

1 

5 

20 

2 

54 

A 

Apr.  17 

1,020 

51 

270 

3 

0 

36 

26 

6 

11 

a  Previous  to  the  experiment  of  Nov.  18,  1915,  with  A,  the  mouthpiece  was  used,  but  on  Nov.  18 
and  thereafter  the  mask  was  employed.  With  the  mouthpiece,  the  subject  was  in  the  sitting 
position,  except  on  Oct.  5,  1915,  when  he  lay  down;  with  the  mask,  he  lay  on  a  couch,  ex¬ 
cept  on  Nov.  29,  1915,  when  he  sat  in  a  chair. 

6  Subject  in  a  post-absorptive  condition. 

RESULTS  OF  MEASUREMENTS  BEFORE  RECTAL  INJECTION. 

In  those  experiments  in  which  the  mouthpiece  was  used,  there  was  a  half- 
hour  rest  before  the  first  period,  while  in  the  experiments  with  the  mask  the 
measurements  began  as  soon  as  the  subject  lay  down.  In  the  charts  of  the 
mask  experiments  only  the  three  or  four  periods  immediately  before  the  in¬ 
jection  are  included,  although  usually,  as  may  be  seen  from  table  23,  six  or 
more  periods  preceded  the  injection.  The  first  observation  indicated  on  each 
curve  for  the  mask  experiments  was  thus  nearly  a  half  hour  after  the  subject 
lay  down.  The  men  showed  the  same  degree  of  variability  in  all  measure¬ 
ments  which  was  found  with  the  sodium-chloride  solution.  This  was  partic¬ 
ularly  true  of  subject  A,  while  subject  C  was  more  nearly  uniform  in  the 
measurements  from  period  to  period.  These  measurements  were  made  under 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  105 


conditions  which  are  strictly  comparable  with  the  measurements  made  in  the 
pre-injection  periods  of  the  previous  group. 

Pulse-Rate. 

The  average  pulse-rate  in  the  preliminary  periods  with  subject  A  varied 
from  59  beats  per  minute  on  April  17  to  79  beats  per  minute  on  October  27. 
When  the  subject  came  to  the  Laboratory  on  October  27,  he  was  emotionally 
disturbed  and  was  thus  not  in  an  ideal  condition  for  an  experiment  of  this 
character.  The  results  show  very  clearly  the  influence  of  the  disturbed 
psychic  condition  upon  the  pulse-rate,  and  likewise  upon  the  metabolism  as 
represented  by  the  oxygen  absorption.  The  pulse-rate  was  unusually  high 
at  the  beginning  of  the  experiment,  but  fell  gradually  during  the  evening. 
The  oxygen  consumption  remained  at  a  high  level  throughout  the  experi¬ 
ment,  with  but  little  permanent  change  from  the  preliminary  values.  These 
results  illustrate  the  necessity  for  assurance  that  the  subject  is  in  a  quiet 
emotional  condition  in  order  that  true  values  may  be  obtained  for  compari¬ 
son  with  those  found  in  studying  a  superimposed  factor.  This  is  in  line  with 
the  recommendation  repeatedly  made  in  publications  from  this  Laboratory 
as  to  ideal  conditions  for  the  determination  of  basal  metabolism.  The  second 
highest  average  pulse-rate  before  injection  in  the  series  with  A  was  73  beats. 
In  the  majority  of  the  experiments  with  this  subject,  the  preliminary  pulse- 
rate  was  not  far  from  that  obtained  under  basal  (post-absorptive)  conditions 
on  October  12,  i.  e.,  64  beats  per  minute.  Subject  C  varied  in  the  prelimi¬ 
nary  period  from  64  beats  to  69  beats  which  approximated  his  basal  pulse-rate 
on  October  24.  The  pulse-rate  in  the  two  experiments  with  subject  D  aver¬ 
aged  before  injection  80  and  84  beats,  respectively.  This  subject  was  char¬ 
acterized  by  a  high  pulse-rate  in  all  his  experiments. 

Oxygen  Absorption. 

With  the  exception  of  October  27,  the  oxygen  absorption  of  subject  A  in 
the  periods  before  injection  varied,  on  the  average,  from  186  to  209  c.  c.  per 
minute;  on  October  27  the  average  value  was  239  c.  c.  As  brought  out  in  the 
discussion  of  the  pulse-rate,  the  experiment  on  October  27  illustrates  clearly 
the  necessity  in  metabolism  studies  of  having  the  subject  tranquil,  since  a 
disturbed  mental  condition  may  result  in  a  disturbed  metabolism.  In  most 
of  the  other  experiments  with  A,  the  preliminary  values  were  not  far  from  the 
basal  oxygen  consumption  obtained  on  October  12,  which  was  209  c.  c. 

With  subject  C  the  oxygen  absorption  varied  on  the  average  before  injec¬ 
tion  from  278  to  291  c.  c.  per  minute;  the  basal  (post-absorptive)  value  on 
October  24  was  280  c.  c.  The  range  in  oxygen  absorption  in  the  preliminary 
periods  of  this  series  of  experiments  with  subject  C  was  narrower  than  that  in 
the  experiments  with  the  sodium-chloride  solution. 

With  subject  D  the  average  values  for  the  preliminary  periods  in  the  two 
experiments  are  224  c.  c.  and  231  c.  c.  per  minute,  which  was  lower  than  the 
oxygen  absorption  (250  c.  c.)  in  the  one  experiment  with  the  sodium  chloride. 
We  have  no  basal  experiment  with  this  subject. 

Respiratory  Quotient. 

With  subject  A  on  November  24  and  December  2,  the  average  values  be¬ 
fore  injection  are  rather  high,  namely,  0.86  and  0.88.  The  last  food  taken 
before  the  experiments  on  these  days  was  at  8  and  10  a.  m.,  respectively. 


106 


HUMAN  METABOLISM  WITH  ENEMATA. 


We  see  no  cause  for  these  high  respiratory  quotients  previous  to  injection. 
The  other  preliminary  values  for  this  subject  range  from  0.76  to  0.82. 

With  subject  C  the  quotients  ranged  before  injection  from  0.84  to  0.77. 
With  subject  D  they  averaged  0.81  and  0.78.  With  the  exception  of  0.76, 


SUBJECT  A.  OCT.  8,  1915 

220  c.c.  5  PER  CENT  ALCOHOL 


MOUTHPIECE 


6U6JECT  A.  OCT  1915 
"220  c.  c  5  PER  CENT  ALCOHOL 


0.85 

0.80 

075 

070 

200 

175 

60 

56 


MOUTHPIECE 


fl 

IESPIRA 

rORY  Q 

JOTIEN 

/  ‘ 

• 

t 

r 

p 

/i 

LA 

/ 

/ 

Vj~J 

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IINUTE, 

P  P  _ 

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,  r 

r\ 

1, 

>ULSE  F 

/" 

ER  MIN 

ITF 

-f 

,n 

. . 

’ 

7" - 

*V  1 — 

3  4  5  6 

HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 

24 


0.85 

0.80 

0.75 

225 

200 

175 

75 

70 

65 


.RESPIRATORY  quotient. 

=  At 


_o2per  MINUTE. c.c.. 


f-=\s 


.PULSE  PER  MINUTE 


— 

"1 

0  1  2  3  4  5  6 

HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 

25 


Fig.  24 — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  October  5,  1915, 
before  and  after  rectal  injection  of  220  c.  c.  of  a  5  per  cent  alcohol  solution.  (Mouth¬ 
piece,  with  intermittent  observation.) 

The  solid  portions  of  the  three  curves  represent  the  averages  for  the  periods,  and  the  broken 
portions  the  intervals  between  observations.  This  applies  to  all  subsequent  experiments  with 
the  mouthpiece. 

Fig.  25. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  October  8,  1915, 
before  and  after  rectal  injection  of  220  c.  c.  of  a  5  per  cent  alcohol  solution.  (Mouth¬ 
piece,  with  intermittent  observation.) 


SUBJECT  A  OCT  12  1915 
320  c.c  5  PER  CENT  ALCOHOL 


MOUTHPIECE 


RESP 

RATORV 

QUOTI 

ENT 

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* 

% 

0  75 
225 
200 
70 
65 
60 


0  12  3  4  5  6 

HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


10 


Fig.  26. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject 
A,  October  12, 1915,  before  and  after  rectal  injection  of  320  c.  c.  of  a  5  per 
cent  alcohol  solution.  (Mouthpiece,  with  intermittent  observation.) 


0.77,  and  0.78  noted  above,  the  respiratory  quotients  for  the  periods  preced¬ 
ing  injection  in  this  series  with  a  5  per  cent  alcohol  solution  are  very  near  the 
normal  values  for  a  post-absorptive  or  basal  condition.  While  some  quo¬ 
tients  are  slightly  lower  than  would  be  expected,  it  is  seen  from  the  experi- 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  107 


ments  with  the  sodium-chloride  solution  that  the  respiratory  quotient  in  the 
evening  tends  to  be  low,  with  a  gradual  increase  throughout  the  whole  night, 
and  it  is  quite  likely  that  the  conditions  were  the  same  in  this  respect  in  both 
series. 


SUBJECT  A.  NOV.  10.  1915 

320  c.  c.  5  PER  CENT  ALCOHOL  MOUTHPIECE 


27  28 

Fig.  27. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  October  27,  1915, 
before  and  after  rectal  injection  of  300  c.  c.  of  a  5  per  cent  alcohol  solution.  (Mouthpiece, 
with  intermittent  observation.) 

Fig.  28. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  November  10, 
1915,  before  and  after  rectal  injection  of  320  c.  c.  of  a  5  per  cent  alcohol  solution.  (Mouth¬ 
piece,  with  intermittent  observation.) 


SUBJECT  C.  OCT  24.  1915 
325  c.  c.  5  PER  CENT  ALCOHOL 


60 


MOUTHPIECE 


RESPIRATC 

)RY  QUC 
rH 

JTIENT 

J  - 1_ 1 

_r 

j 

IUTE,  c.  i 

— i 

/i 

\ r 

-'“K 

PULSE  PE 

— 

3  MINU' 

E 

*■■■  s, 

L_ . — 

TL... 

1  2  3 

HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 

29 


SUBJECT  C  OCT.  29.  1915 
320  c.  c.  5  PER  CENT  ALCOHOL 


MOUTHPIECE 


0.80 

0.75 

300 

275 

70 

65 


O  1  ,2  3  4  5  6 

HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 

30 


l  i  i  r 

RESPIRATORY  QUOTIENT 

L 

~\  ^ 

02PER  f 

-  1 

1INUTE; 

r.  >.  _  _ 

-n. 

-- 

PULSE  1 

fX-j 

>ER  MU' 

& 

IITF 

........ 

........ - 

- 1 

n 

T  h 

Fig.  29. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  C,  October  24, 
1915,  before  and  after  rectal  injection  of  325  c.  c.  of  a  5  per  cent  alcohol  solution.  (Mouth¬ 
piece,  with  intermittent  observation.) 

Fig.  30. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  C,  October  29, 
1915,  before  and  after  rectal  injection  of  320  c.  c.  of  a  5  per  cent  alcohol  solution.  (Mouth¬ 
piece,  with  intermittent  observation.) 


108  HUMAN  METABOLISM  WITH  ENEMATA. 


RESULTS  OF  MEASUREMENTS  AFTER  RECTAL  INJECTION  OF  A  5  PER  CENT 

ALCOHOL  SOLUTION. 

Experiments  with  200  Cubic  Centimeters. 

The  general  course  of  the  pulse-rate,  respiratory  quotient,  and  oxygen 

absorption  in  the  two  experiments  with  subject  A  was  practically  the  same 

as  that  found  when  a  solution  of  sodium  chloride  was  injected.  While  there 


SUBJECT  A  NOV  ia  1915 


SUBJECT  C  NOV  a  1915  400  cc  5  PERCENT  ALCOHOL  MASK 


31  32 


Fig.  31. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  C,  November  8, 
1915,  before  and  after  rectal  injection  of  320  c.  c.  of  a  5  per  cent  alcohol  solution.  (Mouth¬ 
piece,  with  intermittent  observation.) 

Fig.  32. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  November  18, 
1915,  before  and  after  rectal  injection  of  400  c.  c.  of  a  5  per  cent  alcohol  solution.  (Mask, 
with  continuous  observation.) 


SUBJECT  A  NOV.  24.  1915 
420c.c.  5  PERCENT  ALCOHOL 


MASK 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 

33 


SUBJECT  A  DEC.  2.  1915 
420  c.c.  5  PERCENT  ALCOHOL 


MASK 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 

34 


Fig.  33. — Respiratory  quotient,  and  oxygen  absorption  of  subject  A,  November  24,  1915,  before 
and  after  rectal  injection  of  420  c.  c.  of  a  5  per  cent  alcohol  solution.  No  pulse  records  made. 
(Mask,  with  continuous  observation.) 

Fig.  34. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  December  2, 
1915,  before  and  after  rectal  injection  of  420  c.  c.  of  a  5  per  cent  alcohol  solution.  (Mask, 
with  continuous  observation.) 

were  marked  variations  from  time  to  time  in  all  the  factors,  these  were 
apparently  due  to  sleep  or  drowsiness  rather  than  to  the  alcohol  solutions. 
From  these  two  experiments  alone  it  may  be  stated  that  the  injection  into 
the  rectum  of  200  c.  c.  of  a  5  per  cent  alcohol  solution,  i.  e.,  10  grams  of 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  109 


absolute  ethyl  alcohol,  produces  no  change  in  the  three  factors  observed, 
namely,  respiratory  quotient,  oxygen  absorption,  and  pulse-rate. 

Experiments  with  300  Cubic  Centimeters. 

The  results  of  a  larger  number  of  experiments  with  300  c.  c.  of  a  5  per  cent 
alcohol  solution  are  available  for  comparison,  there  being  three  each  with 
subjects  A  and  C. 

With  subject  A  the  respiratory  quotient  was  practically  unaltered  by  the 
alcohol.  The  only  possible  exception  to  this  was  on  October  12,  when  there 
was  a  fall,  which  occurred  about  2  hours  after  the  beginning  of  the  injection, 
and  coincided  with  a  fall  in  pulse-rate.  With  a  later  high  pulse-rate,  how¬ 
ever,  the  respiratory  quotient  was  at  a  low  level.  The  oxygen  absorption 


SUBJECT  C.  NOV  29,  1915 

420  c.  c.  5  PER  CENT  ALCOHOL  MASK 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 

35 


SUBJECT  A.  APR,  3.  1916 

510  c  c.  5  PER  CENT  ALCOHOL  MASK 


36 


Fig.  35. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  C,  November  29, 
1915,  before  and  after  rectal  injection  of  420  c.  c.  of  a  5  per  cent  alcohol  solution.  (Mask, 
with  continuous  observation.) 

Fig.  36. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  April  3,  1916, 
after  rectal  injection  of  510  c.  c.  of  a  5  per  cent  alcohol  solution.  (Mask,  with  continuous 
observation.) 

The  horizontal  line  at  the  bottom  of  this  and  subsequent  charts  gives  a  record  of  sleep,  the 
solid  portions  indicating  when  the  subject  was  asleep,  and  the  broken  portions  when  he 
was  awake. 


fell  off  very  slightly  in  two  experiments  in  about  the  same  manner  as  with  a 
sodium-chloride  solution.  The  pulse-rate  fell  slightly  not  only  on  October 
12,  but  also  on  October  27.  From  the  experiments  with  subject  A,  it  is 
questionable  whether  the  conclusion  can  be  drawn  that  the  injection  of  15 
grams  of  alcohol  in  a  5  per  cent  solution  introduced  rectally  produced  any 
specific  effect,  especially  as  the  results  were  more  or  less  complicated  by 
drowsiness. 

In  the  three  experiments  with  subject  C  the  oxygen  absorption  and  pulse- 
rate  were  practically  unaltered  by  the  alcohol  injection.  There  was  a  slight 
fall  in  the  respiratory  quotient  in  the  three  experiments,  and  as  this  fall  was 
not  accompanied  by  a  similar  lowering  in  pulse-rate,  it  was  probably  due  to 
the  effect  of  alcohol  upon  the  metabolism.  These  experiments  with  C  indi¬ 
cate  a  slight  effect  upon  the  character  of  the  metabolism  after  the  giving 
of  300  c.  c.  of  a  5  per  cent  alcohol  solution  by  rectum. 


no 


HUMAN  METABOLISM  WITH  ENEMATA. 


Experiments  with  400  Cubic  Centimeters. 

Of  the  four  experiments  with  approximately  400  c.  c.,  three  were  with 
subject  A  and  one  with  subject  C.  On  November  18  and  December  2,  sub¬ 
ject  A  was  asleep  the  greater  part  of  the  experiment;  on  November  24  there 
was  some  disquiet  due  to  trouble  with  the  mask.  In  one  of  the  experiments 
with  subject  A,  the  respiratory  quotient  was  practically  unchanged.  In 
the  other  two  there  was  a  fall,  particularly  in  the  experiment  of  December  2, 
one  hour  after  the  beginning  of  the  injection.  The  fall  in  respiratory  quo¬ 
tient  was  accompanied  by  a  rise  in  the  pulse-rate.  In  the  experiments  with 
the  sodium-chloride  solution,  a  fall  in  the  respiratory  quotient  was  usually 
accompanied  by  a  fall  in  the  pulse-rate,  which  was  due  to  drowsiness.  When, 
however,  there  is  a  fall  in  the  respiratory  quotient  which  logically  would  be 
expected  when  alcohol  is  burned,  and,  at  the  same  time,  there  is  a  rise  in  the 
pulse-rate  which  has  been  shown  by  previous  work  to  occur  after  alcohol  has 
been  given,  we  are  led  to  the  conclusion  that  the  two  changes,  that  is,  the 
lowering  of  the  respiratory  quotient  and  the  increase  in  the  pulse-rate,  are 
due  to  the  taking  of  the  alcohol. 


SUBJECT  CX  FEB.  25.  1916 

510  o.  c.  5  PER  CENT  ALCOHOL  MASK 


37  38 

Fig.  37. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  D,  February  18, 
1916,  before  and  after  the  rectal  injection  of  520  c.  c.  of  a  5  per  cent  alcohol  solution.  (Mask, 
with  continuous  observation.) 

Fig.  38. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  D,  February  25, 
1916,  before  and  after  rectal  injection  of  510  c.  c.  of  a  5  per  cent  alcohol  solution.  (Mask, 
with  continuous  observation.) 

The  oxygen  consumption  was  actually  higher  in  all  three  experiments 
after  the  injection  of  alcohol  than  before,  and  in  all  probability  the  rise,  at 
least  some  part  of  it,  was  due  to  the  alcohol.  The  change  in  pulse-rate  on 
November  18,  if  any,  was  in  the  direction  of  acceleration.  On  December  2 
there  was  a  gradual  increase  in  the  pulse-rate  from  the  beginning  to  the  end 
of  the  experiment.  Owing  to  the  non-functionating  of  the  recording  ap¬ 
paratus  no  measurements  could  be  made  of  the  pulse-rate  on  November  24. 
We  have,  then,  with  subject  A  and  400  to  420  c.  c.  of  a  5  per  cent  alcohol 
solution,  two  experiments  (November  18  and  24)  in  which  the  influence  of 
the  alcohol  was  slightly  noticeable,  and  one  experiment  (December  2)  in 
which  there  was  a  consistent  influence,  namely,  a  decrease  in  the  respiratory 
quotient  and  an  increase  in  the  pulse-rate. 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  Ill 


The  experiment  with  subject  C  with  420  c.  c.  of  a  5  per  cent  alcohol  solution 
exhibited  a  tendency  in  the  same  direction  as  those  with  subject  A,  but 
slight  activity  may  have  played  a  role. 

Experiments  with  500  to  1,000  Cubic  Centimeters. 

Three  experiments  were  made  with  500  c.  c.  of  a  5  per  cent  alcohol  solu¬ 
tion,  one  with  subject  A  and  two  with  subject  D.  In  the  experiment  with 
A  the  subject  was  asleep  the  whole  of  the  experimental  period.  After  the 
first  hour  there  was  a  marked  fall  in  the  respiratory  quotient.  Unfortu¬ 
nately,  there  were  no  preliminary  periods  in  this  experiment  with  which  the 
results  can  be  compared,  but  judging  by  other  experiments  in  which  alcohol 
was  given  by  rectum,  it  is  reasonable  to  assume  that  this  fall  is  a  positive 
change  due  to  the  influence  of  the  alcohol,  as  its  effect  does  not  usually  be¬ 
come  apparent  until  after  the  first  hour.  The  pulse-rate  rose  slightly  during 
the  experiment.  The  oxygen  absorption  fell  slightly  during  the  first  1J 
hours  and  was  constant  thereafter  until  the  very  last  period. 


SUBJECT  A.  APR.  17.  1916 

520  c.c,  5  PERCENT  ALCOHOL  +  5  100  c.c.  PORTIONS  MASK 


Fig.  39. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  April 
17,  1916,  before  and  after  rectal  injection  of  520  c.  c.  of  a  5  per  cent  alcohol  solu¬ 
tion,  followed  by  five  100  c.  c.  portions,  with  a  total  injection  of  1,020  c.  c.  over  a 
period  of  A\  hours.  (Mask,  with  continuous  observation.) 


In  the  experiments  with  subject  D  on  February  18  and  25,  the  conditions 
as  to  sleep  were  very  variable,  which  makes  comparison  between  the  results 
obtained  before  and  after  alcohol  difficult.  The  subject  was  quiet  in  both 
experiments.  The  course  of  the  respiratory  quotient  was  very  irregular  and 
the  changes  are  not  clearly  attributable  to  the  effect  of  the  alcohol,  excepting 
possibly  those  which  occurred  in  the  last  few  periods  of  the  experiment  on 
February  18.  The  oxygen  absorption  in  neither  experiment  was  influenced 
by  the  alcohol.  The  pulse-rate  was  affected  to  some  extent,  apparently,  in 
the  experiment  on  February  18,  but  on  February  25  there  was  no  change. 
Here  again  is  a  condition  when  one  experiment  with  a  subject  shows  no  effect 
and  the  other  exhibits  a  specific  influence  on  the  respiratory  quotient  and  the 
pulse-rate,  decreasing  the  one  and  increasing  the  other. 


112 


HUMAN  METABOLISM  WITH  ENEMATA. 


There  was  only  one  experiment  with  1,000  c.  c.  of  a  5  per  cent  solution  of 
alcohol.  The  most  noticeable  effect  of  this  injection  was  upon  the  pulse- 
rate,  which  changed  from  a  level  of  58  beats  before  the  alcohol  was  given  to 
78  beats  6  hours  after  the  injection  began.  Although  affected  by  varying 
amounts  of  sleep,  the  course  of  the  pulse-rate  was  evidently  affected  by  the 
alcohol  given.  The  respiratory  quotient  fell  after  2  hours  and  the  oxygen 
was  slightly  increased. 


DISCUSSION  OF  COMPOSITE  CHART. 

In  figure  40  is  a  composite  chart  for  the  experiments  with  a  5  per  cent 
alcohol  solution,  which  has  been  drawn  in  the  same  manner  as  the  chart  for 
the  sodium-chloride  experiments.  As  many  of  these  alcohol  experiments 
were  of  longer  duration  than  the  sodium-chloride  experiments,  the  chart  has 
been  extended  so  as  to  represent  4  hours  after  the  rectal  injection  began. 
The  duration  of  the  preliminary  period  is  the  same  as  that  for  the  preceding 
series  (40  minutes).  All  of  the  experiments  except  that  with  a  solution  of 
1,020  c.  c.  are  included  in  this  composite.  This  experiment  is  omitted  be¬ 
cause  of  the  larger  quantity  of  alcohol  and  the  long  period  of  injection. 


Fig.  40. — Chart  showing  com¬ 
posite  results  for  measurements 
of  respiratory  quotient,  oxygen 
absorption,  and  pulse-rate  in 
15  experiments  with  rectal  in¬ 
jection  of  11  to  26  grams  of 
alcohol  in  a  5  per  cent  solution. 
(Mouthpiece  or  mask.) 


COMPOSITE  CHART 


s^RESf 

’IRATOR 

< 

o 

c 

o 

—1 

■jENT 

-  O  PF 

:r  MINI 

TP  ^  o  - 

PUL 

SE  PER 

minut 

70 

65 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


8 


Pulse-rate. — The  preliminary  pulse-rate  in  these  alcohol  experiments  was 
slightly  higher  than  that  with  the  sodium-chloride  solution,  being  about  71 
beats  at  the  beginning  and  falling  to  67  beats  before  the  injection  began.  It 
rose  within  the  first  half  hour  after  injection  and  continued  rising  gradually 
for  2\  hours  after  injection,  to  a  maximum  of  72  beats,  i.  e.,  an  increase  of  5 
beats  over  that  at  the  end  of  the  preliminary  period.  This  level  was  main¬ 
tained  for  some  time  and  then  the  pulse-rate  began  to  fall.  Even  at  the  end 
of  4  hours  the  rate  was  still  higher  than  when  the  injection  began.  This  is  in 
contrast  to  the  results  obtained  in  the  sodium-chloride  experiments,  in  which 
the  pulse-rate  gradually  fell.  With  the  sodium-chloride  solution,  the  pulse- 
rate  was  62  beats  at  the  end  of  2  hours;  with  the  5  per  cent  alcohol  solution 
it  was  71  beats  at  the  end  of  2  hours.  There  was  accordingly  a  difference  in 
level  of  9  beats.  It  must  be  noted  here  again  that  this  chart  includes  alco¬ 
hol  experiments  with  the  smaller  quantities  of  alcohol  in  which  there  was 
slight,  if  any,  influence,  as  well  as  those  with  larger  quantities  in  which  the 
influence  was  more  marked. 

Oxygen  absorption. — The  oxygen  absorption  in  the  preliminary  period  of 
this  series  was  about  the  same  as  in  the  sodium-chloride  experiments,  namely, 
237  c.  c.  It  did  not  change  materially  until  the  second  half  hour  after  in- 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  113 


jection,  when  it  began  to  rise  slightly,  with  a  maximum  increase  of  about  8 
c.  c.  This  level  was  maintained  throughout  the  remaining  3  hours  after  in¬ 
jection.  This  is  in  contrast  to  the  average  oxygen  absorption  with  the 
sodium-chloride  injection,  which  gradually  fell  in  the  second  and  third  hours 
after  injection. 

Respiratory  quotient. — The  respiratory  quotient  with  the  5  per  cent  alcohol 
solution  averaged  about  0.80  during  the  preliminary  period.  It  then  fell 
about  0.02  during  the  second  half  hour  after  injection,  and  remained  at  this 
level  for  the  remaining  3  hours  of  the  experiments. 

This  composite  chart  shows,  therefore,  that  there  was  a  definite,  though 
slight,  influence  as  a  result  of  the  injection  of  a  5  per  cent  alcohol  solution  in 
quantities  varying  from  200  to  500  c.  c.  It  must  be  noted  here  again  that 
the  chart  includes  experiments  in  which  the  amounts  given  were  so  small  that 
the  effect  was  slight  and  when  superimposed  upon  the  total  values  of  pulse- 
rate,  oxygen  absorption,  and  respiratory  quotient,  the  influence  could  not  be 
detected.  Because  with  200  c.  c.  of  a  5  per  cent  alcohol  solution  the  effect 
was  not  clearly  apparent,  one  must  not  suppose  that  there  was  no  utilization 
of  alcohol.  If  a  subject  were  available  who  could  maintain  an  even  metab¬ 
olism  and  an  unaltered  degree  of  wakefulness  as  well  as  of  quietness,  it  is 
probable  that  quantities  as  small  as  200  c.  c.  would  show  a  definite  utilization. 

GENERAL  CONCLUSIONS  REGARDING  EXPERIMENTS  WITH  A  5  PER  CENT 

ALCOHOL  SOLUTION. 

It  must  be  admitted  that  the  experiments  in  this  series  are  hardly  sufficient 
in  number  for  the  drawing  of  very  definite  conclusions  with  each  quantity 
regarding  the  effect  upon  the  pulse-rate,  oxygen  absorption,  and  respiratory 
quotient  of  the  rectal  introduction  of  a  5  per  cent  alcohol  solution.  The 
general  statement  may  be  made  that  200  c.  c.  had  no  measurable  effect 
upon  these  factors;  that  300  c.  c.,  given  to  two  subjects,  produced  a  slight 
lowering  of  the  respiratory  quotient  with  one  of  them;  that  400  c.  c.  in  4 
experiments  tended  to  lower  the  respiratory  quotient  and  raise  the  pulse- 
rate  and  oxygen  absorption;  and  that  500  c.  c.  in  2  out  of  3  experiments  had 
the  characteristic  alcohol  effect,  fall  in  the  respiratory  quotient  and  rise  in 
the  pulse-rate.  Solutions  in  quantities  of  500  c.  c.  or  under,  containing  5 
per  cent  alcohol,  may  cause  the  pulse-rate  and  oxygen  absorption  to  rise 
slightly  and  the  respiratory  quotient  to  fall  significantly.  The  one  experi¬ 
ment  with  1,000  c.  c.  shows  a  definite  fall  in  the  respiratory  quotient  after 
2  hours.  The  pulse-rate  began  to  rise  in  1J  hours,  while  the  oxygen  absorp¬ 
tion  was  slightly  increased  at  the  end  of  2  hours.  It  is  surprising  that  the 
effect  is  not  more  marked  with  this  quantity  of  alcohol.  The  general  pic¬ 
ture  of  this  group  of  alcohol  experiments  therefore  differs  from  that  found 
with  the  sodium-chloride  solution.1 

1  The  sodium-chloride  experiments  were  made  primarily  to  obtain  the  course  of  the  metabolism 
during  this  period  of  the  day  and  also  to  determine  whether  the  rectal  injection  of  a  solution, 
which  presumably  of  itself  has  no  influence  upon  the  metabolism,  would,  in  any  way,  alter 
its  general  course.  Therefore,  we  use  the  results  of  these  experiments  as  a  contrast,  or  for 
comparison  purposes,  with  the  experiments  when  alcohol  was  taken  by  rectum.  It  was 
shown  in  the  sodium-chloride  experiments  that  the  respiratory  quotient  either  tended  to 
remain  unaltered  or  else  it  declined  slightly  during  the  evening  session,  but  at  no  point  was 
this  decline  sharp.  The  figures  for  oxygen  absorption  were  inclined  to  remain  unaltered  or 
to  be  lowered  slightly,  while  the  pulse-rate  showed  in  general  a  gradual  decline  through 
the  evening. 


114 


HUMAN  METABOLISM  WITH  ENEMATA. 


Experiments  with  a  7.5  per  cent  Alcohol  Solution. 

A  number  of  experiments  were  carried  out  in  which  the  solution  used  for 
rectal  injection  contained  7.5  per  cent  alcohol  by  weight.  The  volume  of  the 
solution  varied.  In  three  experiments  265  c.  c.  of  a  7.5  per  cent  alcohol 
solution  were  used,  this  amount  containing  19.9  grams  of  alcohol.  One  ex¬ 
periment  was  made  with  350  c.  c.,  or  26.3  grams  of  alcohol,  and  another  with 
415  c.  c.,  or  31.1  grams  of  alcohol.  In  two  experiments  approximately  500 
c.  c.  of  a  7.5  per  cent  alcohol  solution  were  given,  or  37.5.  grams  of  alcohol. 
In  one  experiment  with  subject  C  on  April  18,  510  c.  c.  of  a  7.5  per  cent  alco¬ 
hol  solution  were  first  given  and  then  6  portions  of  50  c.  c.  each  of  the  same 
concentration  were  added,  or  a  total  amount  of  810  c.  c.,  i.  e.,  60.8  grams. 


Table  24. — Statistics  of  respiratory  exchange  observations  before  and  after  the  injection  by 

rectum  of  a  7.5  per  cent  alcohol  solution. 


Subject. 

Date.0 

Alcohol 

injected. 

Duration 

of 

injection. 

Periods  before 
injection. 

Periods  after 
injection. 

Volume 

of 

solution. 

Weight 

of 

alcohol. 

No. 

Time 

covered. 

No. 

Time 

covered. 

1916. 

c.  c. 

Qm. 

min. 

h. 

min. 

h. 

min. 

A 

Feb.  28 

265 

19.9 

18 

10 

0 

54 

25 

3 

19 

C 

Mar.  1 

265 

19.9 

18 

4 

0 

40 

16 

2 

40 

D 

Mar.  3 

265 

19.9 

26 

4 

0 

40 

23 

4 

2 

A 

Apr.  10 

350 

26.3 

31 

3 

0 

30 

26 

4 

49 

C 

Mar.  22 

415 

31.1 

20 

6 

1 

00 

19 

3 

10 

A 

Apr.  15 

500 

37.5 

29 

4 

0 

40 

19 

3 

41 

C 

Mar.  29 

510 

38.3 

(?) 

0 

0 

00 

27 

4 

44 

Apr.  18 

6  810 

60.8 

286 

2 

0 

26 

24 

5 

33 

1917. 

A 

Jan.  20-21 

500 

37.5 

76 

3 

1 

33 

10 

6 

52 

Feb.  3-  4 

500 

37.5 

82 

3 

1 

17 

12 

7 

5 

Feb.  15—16 

500 

37.5 

118 

4 

2 

5 

10 

7 

8 

Mar.  2-  3 

500 

37.5 

152 

0 

0 

00 

15 

8 

5 

Mar.  23-24 

500 

37.5 

121 

3 

1 

31 

13 

6 

32 

°  The  gasometer  and  mask,  with  the  subject  in  the  lying  position,  were  used  in  all  but  the  1917 
experiments  with  A.  In  these  5  experiments,  the  observations  were  carried  on  through¬ 
out  the  night  with  the  clinical  respiration  chamber  and  the  subject  in  the  lying  position. 

6  Given  in  7  portions,  i.  e.,  510  c.  c.  in  the  first  injection,  followed  at  intervals  by  6  portions  of  50 
c.  c.  each. 

All  of  these  experiments  were  carried  out  by  the  usual  gasometer  and  mask 
method,  with  the  subject  lying  on  a  couch,  and  continuous  observations. 
The  sleep-recording  device  was  also  used.  In  addition  to  these  observations, 
5  experiments  were  made  with  the  clinical  respiration  chamber,  in  which  500 
c.  c.  of  a  7.5  per  cent  alcohol  solution  were  injected.  Of  the  13  experiments, 
A  served  as  subject  in  8,  C  in  4,  and  D  in  1.  The  statistics  regarding  the 
observations  with  a  7.5  per  cent  alcohol  solution  are  given  in  table  24, 
grouped  according  to  the  amount  given  and  the  apparatus  employed.  The 
experiments  with  the  gasometer  method  are  first  discussed. 

OBSERVATIONS  WTTH  GASOMETER  AND  MASK  METHOD. 

Results  of  Measurements  Before  Rectal  Injection. 

These  experiments  were  carried  out  under  practically  the  same  conditions 
as  those  for  the  two  previous  groups,  that  is,  the  subject  came  in  the  latter 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  115 


part  of  the  afternoon,  having  had  a  meal  either  in  the  morning  or  at  noon. 
The  latest  time  at  which  food  was  taken  was  2  p.  m.  (C,  March  1  and  March 
22)  and  the  nearest  to  the  experimental  period  was  7h  30m  a.  m.  (C,  April 
18)  with  the  first  period  of  the  experiment  beginning  at  10h  03m  a.  m. 
The  graphic  records  of  the  results  are  given  in  figures  41  to  48. 


SUBJECT  A,  FEB.  28.  1916 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


SUBJECT  C.  MAR.  1.  1916 

265  c.c.  7.5  PERCENT  ALCOHOL  MASK 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


41  42 

Fig.  41. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  February  28, 
1916,  before  and  after  rectal  injection  of  265  c.  c.  of  a  7.5  per  cent  alcohol  solution.  (Mask, 
with  continuous  observation.) 

The  horizontal  line  at  the  bottom  of  this  and  subsequent  charts  gives  a  record  of  sleep, 
the  solid  portions  indicating  when  the  subject  was  asleep  and  the  broken  portions  when  he 
was  awake. 

Fig.  42. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  C,  March  1,  1916, 
before  and  after  rectal  injection  of  265  c.  c.  of  a  7.5  per  cent  alcohol  solution.  (Mask,  with 
continuous  observation.) 


SUBJECT  D.  MAR.  3.  1916 

265  c.  c.  7.5  PER  CENT  ALCOHOL  MASK 


Fig.  43. — Respiratory  quotient,  oxygen  absorption,  and  pulse- 
rate  of  subject  D,  March  3,  1916,  before  and  after  rectal 
injection  of  265  c.  c.  of  a  7.5  per  cent  alcohol  solution. 
(Mask,  with  continuous  observation.) 


116 


HUMAN  METABOLISM  WITH  ENEMATA. 


Pulse-rate. — The  average  pulse-rate  for  subject  A  in  the  preliminary  pe¬ 
riods  of  the  three  experiments  varied  from  64  to  68  beats,  this  being  very 
close  to  his  basal  pulse-rate  of  64  beats.  With  C  the  average  varied  from  59 
on  March  22  to  76  beats  on  April  18.  No  cause  is  known  for  the  high  pulse- 
rate  with  C  on  April  18.  In  the  one  experiment  with  D,  the  average  pulse- 
rate  for  the  preliminary  periods  was  78  beats  which  is  about  this  subject’s 
rate  in  the  waking  condition. 

Oxygen  absorption. — The  oxygen  absorption  for  subject  A  varied  on  the 
average  in  the  preliminary  periods  from  181  c.  c.  per  minute  on  April  10  to 
215  c.  c.  per  minute  on  April  15;  with  subject  C,  the  average  preliminary 
values  ranged  from  264  to  281  c.  c.;  with  subject  D,  the  average  preliminary 
oxygen  absorption  was  239  c.  c. 


SUBJECT  A.  APR.  10,  1916 

350  c.  c.  7.5  PER  CENT  ALCOHOL  MASK 


Fig.  44. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of 
subject  A,  April  10,  1916,  before  and  after  rectal  injection  of  350 
c.  c.  of  a  7.5  per  cent  alcohol  solution.  (Mask,  with  continuous 
observation.) 

Respiratory  quotient. — The  average  respiratory  quotient  with  subject  A 
was  0.83  in  the  preliminary  periods  for  all  the  experiments.  Subject  C 
varied  from  0.80  on  April  18  to  0.90  on  March  1.  No  particular  reason  is 
known  for  the  high  average  respiratory  quotient  with  this  subject  before  in¬ 
jection  on  March  1.  The  average  preliminary  quotient  for  subject  D  on 
March  3  was  0.78.  Thus,  with  the  exception  of  C  on  March  1,  the  average 
respiratory  quotients  before  injection  were  all  within  the  range  that  might  be 
expected  for  basal  conditions,  although  the  experiments  were  not  strictly 
basal  in  that  they  were  carried  out  usually  in  the  evening  and  within  5  or  6 
hours  of  the  last  meal. 

Results  of  Measurements  After  Rectal  Injection  of  a  7.5  per  cent  Alcohol 

Solution. 

Pulse-rate. — The  pulse-rate  in  practically  all  of  the  experiments  shows  a 
rise  after  injection  which  was  apparently  due  to  the  influence  of  alcohol  in¬ 
jected  rectally.  In  three  experiments  the  subject  was  asleep  most  of  the 
time,  so  that  the  pulse-rate  is  comparable  from  beginning  to  end.  In  all  of 
these  three  experiments  (with  subject  A,  February  28,  April  10,  and  15)  the 
pulse-rate  rose.  With  the  smallest  quantity  of  265  c.  c.,  representing  about 
20  grams  of  alcohol,  there  was  a  positive  rise  of  about  5  beats  per  minute  and 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  117 


increases  of  about  the  same  order  of  magnitude  were  found  in  the  other  two 
experiments. 

Of  the  experiments  in  which  the  subject  was  asleep  only  part  of  the  time, 
that  with  C  on  March  22  gave  the  most  positive  results,  with  a  change  from 
58  beats  when  the  subject  was  asleep  to  about  63  beats  when  he  awoke. 
This  rise  continued  until  it  reached  the  height  of  75  beats  in  the  course  of 
2\  to  3  hours,  thus  indicating  a  very  definite  increase  of  heart-rate  due  to  the 
injection  of  400  c.  c.  of  the  solution,  or  about  30  grams  of  alcohol. 

Three  of  the  other  experiments  (with  subject  C  on  March  1  and  29,  and 
with  subject  D  on  March  3)  likewise  exhibit  increases  in  the  pulse-rate  which 
can  hardly  be  ascribed  solely  to  subjective  impressions  or  to  changes  in  the 
conditions  as  to  sleep.  The  only  experiment  in  which  no  change  due  to  the 
alcohol  is  apparent  is  that  with  C  on  April  18,  which  is  complicated  by  two 
long  periods  of  sleep.  When  the  amount  of  alcohol  given  is  considered,  the 
absence  of  alcohol  effect  is  surprising. 


Fig.  45. — Respiratory  quotient,  oxygen 
absorption,  and  pulse-rate  of  subject 
C,  March  22,  1916,  before  and  after 
rectal  injection  of  415  c.  c.  of  a  7.5 
per  cent  alcohol  solution.  (Mask, 
with  continuous  observation.) 


iSUBJECT  Cl  MAR.  22.  1916 

•415  c.c.  7.5  PER  CENT  ALCOHOL  MASK 


Oxygen  absorption. — 'While  in  some  of  the  experiments  the  injection  of  the 
7.5  per  cent  solution  of  alcohol  produced  a  slight  increase  in  the  oxygen  ab¬ 
sorption,  this  factor  was  apparently  less  influenced  than  any  of  the  three 
measured.  In  the  first  experiment  with  265  c.  c.  (about  20  grams  of  alcohol), 
in  which  subject  A  was  asleep  the  entire  period,  there  was  a  slight  rise  in  the 
oxygen  absorption.  The  same  was  true  with  subject  D  on  March  3  and  with 
subject  A  on  April  10.  In  the  experiment  with  subject  D  on  March  3  there 
was  a  complication  at  the  beginning  of  the  experiment  due  to  sleep,  but  if  the 
period  of  wakefulness  after  the  sleep  is  compared  with  the  period  after  inter¬ 
ruption  due  to  urinating,  it  will  be  seen  that  in  the  latter  case  there  was  a 
slightly  higher  average  oxygen  absorption  than  in  the  period  before  the 
interruption.  With  subject  A,  on  April  10,  the  average  oxygen  absorption 
subsequent  to  the  interruption  due  to  urinating  was  very  materially  higher 
than  that  preceding  it.  It  is  doubtful  if  any  experiments  other  than  those 
cited  show  an  increase  in  the  oxygen  absorption  due  to  the  injection  of  a  7.5 
per  cent  alcohol  solution. 

Respiratory  quotient. — The  respiratory  quotient  in  practically  all  of  the 
experiments  with  a  7.5  per  cent  alcohol  solution,  with  the  exception  of  that 
with  C  on  April  18,  was  found  to  be  from  0.03  to  0.07  or  0.08  lower  after  the 


118 


HUMAN  METABOLISM  WITH  ENEMATA. 


injection.  As  pointed  out  in  the  introduction  of  this  section,  the  theoretical 
effect  of  alcohol  upon  the  respiratory  quotient  when  alcohol  is  utilized  is  a 
depression  of  the  respiratory  quotient  depending  in  extent  upon  the  amount 
of  alcohol  actually  burned.  The  lowering  which  occurs  here  is  thus  in  agree¬ 
ment  with  the  theoretical  possibilities,  and  it  is  evident  from  the  depression 
of  the  respiratory  quotient  that  alcohol  is  utilized  by  the  subject.  This 
lowering  was  evident  even  with  the  smaller  quantities,  namely,  265  c.  c.,  and 
was  very  marked  in  some  of  the  experiments.  The  fall  began  anywhere  from 
lj  to  2  hours  after  the  injection  and  was  apparent  even  when  sleep  occurred 
in  the  preliminary  period  or  in  the  first  part  of  the  experiment  and  was  then 
followed  by  a  period  of  wakefulness.  The  sleep  tended  to  depress  the  quo¬ 
tient  but,  in  spite  of  this,  the  quotient  was  lower  in  periods  in  which  the 
subject  was  awake  than  in  periods  in  which  he  was  asleep,  indicating  that  the 
respiratory  quotient  was  decidedly  depressed  by  the  injection  of  the  7.5  per 
cent  alcohol  solution.  This  effect  was  found  even  when  the  quantities  given 


0.90 

0.85 

0.80 

Fig.  46. — Respiratory  quotient,  oxy¬ 
gen  absorption,  and  pulse-rate  of  0.75 
subject  A,  April  15,  1916,  before 
and  after  rectal  injection  of  500  225 
c.  c.  of  a  7.5  per  cent  alcohol 
solution.  (Mask,  with  continuous  200 
observation.)  75 

70 

65 


were  smaller  than  those  used  with  the  5  per  cent  alcohol  solution.  The  con¬ 
clusion  may  therefore  be  drawn  that  a  7.5  per  cent  alcohol  solution  is  more 
effective  in  lowering  the  respiratory  quotient  when  the  substance  is  injected 
rectally  than  the  same  weight  of  alcohol  in  a  5  per  cent  solution. 

Discussion  of  Composite  Chart  and  General  Conclusions. 

A  composite  chart  giving  average  curves  for  experiments  with  a  7.5  per 
cent  solution  of  alcohol  has  been  prepared  in  the  same  manner  as  those  for  the 
preceding  series  of  experiments.  This  is  given  in  figure  49.  It  includes  only 
those  experiments  with  a  7.5  per  cent  alcohol  solution  in  which  the  mask  and 
gasometer  method  was  used.  It  must  be  noted  that  the  amounts  of  alcohol 
given  in  these  experiments  (from  19.9  to  60.8  grams)  were,  on  the  whole, 
slightly  or  considerably  higher  than  those  in  the  experiments  with  the  5  per 
cent  solution.  We  thus  have  to  consider  both  the  effect  of  concentration  and 
the  effect  of  the  total  amount  of  alcohol. 

Pulse-rate. — The  pulse-rate  for  this  group  of  experiments  was  slightly 
higher  during  the  preliminary  period  than  the  pulse-rate  preceding  the 
sodium-chloride  experiments.  It  was,  however,  about  the  same  as  for  the 


SUBJECT  A,  APR.  15.  1916 

500  c.  c.  7.5  PER  CENT  ALCOHOL  MASK 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  119 


5  per  cent  alcohol  solution.  During  the  preliminary  period  there  was  a 
steady  fall  which  continued  nearly  through  the  first  half  hour  after  injection. 
The  pulse  then  rose  until  it  reached  the  level  of  the  pulse-rate  at  the  beginning 


SUBJECT  C.  MAR.  29  1916 

510  cc  7  5  PERCENT  ALCOHOL  MASK 


Fig.  47. — Respiratory  quotient,  oxygen  absorption,  and  pulse- 
rate  of  subject  C,  March  29,  1916,  after  rectal  injection  of 
510  c.  c.  of  a  7.5  per  cent  alcohol  solution.  (Mask,  with 
continuous  observation.) 


SUBJECT  C  APR.15T916' 

510  c.0.  7.5  PER  CENT  ALCOHOL  +  6  PORTIONS  OF  50  c.c.  MASK 


Fig.  48. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  sub¬ 
ject  C,  April  18,  1916,  before  and  after  rectal  injection  of  510  c.  c.  of 
a  7.5  per  cent  alcohol  solution,  followed  at  intervals  by  six  portions 
of  50  c.  c.  each.  (Mask,  with  continuous  observation.) 

The  first  injection  was  begun  at  10h  22m  a.  m.;  the  subsequent  injec¬ 
tions  of  50  c.  c.  each  began  at  llh  41m  a.  m.,  12b  22m,  lb  07m,  lb  42m, 

2b  22m,  and  2b  55m  p.  m.,  respectively. 

of  the  preliminary  period.  The  average  pulse  during  the  last  3  hours  was 
4  beats  higher  than  the  pulse-rate  at  the  time  of  injection  or  in  the  half  hour 
subsequent  to  it.  In  contrast  to  the  course  of  the  pulse-rate  during  the 


120 


HUMAN  METABOLISM  WITH  ENEMATA. 


sodium-chloride  experiments,  there  was  thus  a  rise  instead  of  a  fall,  indicating 
a  definite  increase  in  pulse-rate  due  to  the  injection  of  a  7.5  per  cent  alcohol 
solution. 

Oxygen  absorption . — The  average  oxygen  absorption  was  about  the  same 
in  the  preliminary  period  as  in  the  two  preceding  composite  charts.  It  began 
rising  immediately  after  the  injection  from  237  c.  c.  to  a  maximum  of  255 
c.  c.  This  increase  was  somewhat  greater  than  that  obtained  with  the  5  per 
cent  alcohol  solution.  At  the  end  of  2\  hours  it  began  to  fall,  but  4  hours 
after  injection  it  had  not  reached  the  level  found  at  the  time  of  injection. 
There  was  accordingly  an  increase  in  the  oxygen  absorption  as  a  result  of 
giving  the  7.5  per  cent  alcohol  solution,  which  took  place  within  an  hour  of 
the  injection.  As  the  calorific  value  of  oxygen  when  used  in  burning  alcohol 
is  4.85  per  liter,  the  same  as  that  for  a  combination  of  fat  and  carbohydrate 
with  a  respiratory  quotient  of  0.84,  this  means  not  only  an  increase  in  oxygen 
absorption,  but  also  an  increase  in  heat  produced. 


Fig.  49. — Chart  showing  com¬ 
posite  results  for  measure¬ 
ments  of  respiratory  quotient, 
oxygen  absorption,  and  pulse- 
rate  in  8  experiments  with 
rectal  injection  of  20  to  60 
grams  of  alcohol  in  a  7.5  per 
cent  solution.  (Mask.) 


COMPOSITE  CHART 

0.85. 


R 

ESPIRA7 

ORY  Ql 

IOTIENT 

- c 

2  PER  M 

INUTE,  c 

.  c. 

p 

JLSS  Pt 

:r  minl 

tf 

70 

65 

60 


0  1  2  3  4  5  6 

HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


"8 


Respiratory  quotient. — The  respiratory  quotient  during  the  preliminary 
period  was  fairly  high,  i.  e.,  about  0.84.  It  gradually  fell  after  the  injection 
of  the  alcohol,  the  fall  continuing  throughout  the  whole  4  hours.  The  quo¬ 
tient  at  the  end  was  0.76,  or  a  decrease  of  0.08  during  the  course  of  4  hours. 
This  indicates  very  clearly  the  utilization  of  alcohol,  for,  if  it  is  used,  the 
respiratory  quotient  will  fall,  as  the  theoretical  respiratory  quotient  of  al¬ 
cohol  is  0.667,  which  is  lower  than  the  respiratory  quotient  for  fat  or  for 
carbohydrate. 

The  general  effect  of  the  introduction  of  a  7.5  per  cent  alcohol  solution  by 
rectum  in  quantities  up  to  800  c.  c.  is  to  increase  the  pulse-rate  and  the 
oxygen  absorption,  and  to  lower  the  respiratory  quotient  in  a  greater  degree 
than  does  500  c.  c.  or  less  of  a  5  per  cent  alcohol  solution.  As  pointed  out 
before,  we  have  to  do  here  with  an  increase  in  both  concentration  and  total 
quantity  of  alcohol.  The  experiments  are  not  sufficient  in  number  or  in 
character,  however,  to  distinguish  between  the  effect  of  greater  quantities  of 
alcohol  and  the  effect  of  greater  concentration. 

OBSERVATIONS  WITH  CLINICAL  RESPIRATION  CHAMBER.1 

In  the  five  experiments  in  which  the  clinical  respiration  chamber  was 
employed,  only  subject  A  was  used  and  500  c.  c.  of  the  7.5  per  cent  alcohol 

i  An  abstract  of  the  results  of  the  measurements  of  the  oxygen  absorption  and  pulse-rate  has  been 
given  by  Miles:  Carnegie  Inst.  Wash.  Pub.  No.  333,  1924,  p.  121. 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  121 


solution  were  injected  in  every  instance.  (See  table  24.)  The  subject  re¬ 
mained  in  the  apparatus  during  the  night  and  the  duration  of  the  injection 
was  longer  than  in  all  but  one  of  the  gasometer  and  mask  experiments  in 
which  the  7.5  per  cent  alcohol  solution  was  used.  The  curve  for  the  carbon- 
dioxide  production  is  added  to  those  for  the  other  factors  in  the  graphic 
records  in  figures  50  to  54.  All  but  one  of  the  experiments  were  preceded  or 
followed  or  both  by  short  observations  with  the  gasometer  and  mask.  The 


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results  of  these  morning  and  evening  experiments  are  given  in  short  curves 
preceding  or  following  the  longer  curves  for  the  night  experiments.  The 
observations  on  February  15-1 6,  March  2-3,  and  March  23-24  were  preceded 
and  followed  by  psychological  tests  connected  with  another  research.  The 
heart-rate  was  also  determined  at  intervals  throughout  the  night  by  means 
of  standard  electro-cardiograms,1  as  was  done  in  certain  of  the  sodium- 


1  For  a  detailed  account  of  these  psychological  tests  and  the  standard  electro-cardiograms,  see 
Miles:  loc.  cit.,  pp.  111-124. 


122 


HUMAN  METABOLISM  WITH  ENEMATA. 


chloride  experiments.  (See  p.  97.)  Accordingly,  in  addition  to  the  pneumo¬ 
graphs  and  stethoscope,  the  subject  wore  cheese-cloth  bandages,  moistened 
in  a  solution  of  sodium  chloride,  around  the  left  ankle  and  the  two  wrists, 
which  were  connected  with  the  rest  of  the  electro-cardiographic  outfit. 

Pulse-rate. — The  pulse-rate  in  the  control  experiments  with  the  clinical 
chamber  rose  or  fell  but  little  during  the  night.  The  mask  was  applied  to 


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the  subjects  in  all  of  the  experiments  with  the  chamber  as  soon  as  possible 
with  minimum  amount  of  effort  on  the  part  of  the  subject,  and  measure¬ 
ments  commenced  immediately.  (See  figs.  20  to  23.)  In  contrast  with  these 
observations,  the  most  striking  results  for  the  chamber  experiments  in 
which  500  c.  c.  of  a  7.5  per  cent  alcohol  solution  (37.5  grams)  were  injected  rec- 
tally  were  found  with  the  pulse-rate.  In  the  five  experiments  this  invari- 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  123 


ably  rose  after  the  injection,  with  a  maximum  increase  of  over  20  beats. 
Although  the  experiments  continued  over  a  period  of  about  7  hours  after 
the  injection  began,  in  only  one  (March  2-3)  was  there  any  indication  of  a 
return  to  the  pre-injection  level.  It  must  also  be  noted  that  this  increase  in 
pulse-rate  occurred  notwithstanding  the  fact  that  the  subject  was  sound 
asleep  practically  the  entire  time. 


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On  January  20-21,  the  average  pulse-rate  before  any  effect  due  to  alcohol 
became  apparent  was  about  56  beats;  it  rose  abruptly  to  65  beats  during  the 
second  hour  after  injection,  and  then  gradually  increased  until  at  the  end  of 
the  sixth  hour  after  injection  it  was  73  beats.  After  the  subject  woke  the 
rate  rose  still  higher  to  79  beats. 

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124 


HUMAN  METABOLISM  WITH  ENEMATA. 


of  the  alcohol  was  about  54  beats.  At  the  end  of  2  hours  it  rose  to  about  60 
beats  and  remained  at  this  level  until  the  subject  awoke  at  the  end  of  the 
sixth  hour,  when  it  rose  to  68  beats  and  later  to  70  beats.  There  was  thus  a 
change  from  54  to  70  beats  in  the  course  of  the  experiment.  The  short 
periods  with  the  mask  in  the  morning  had  about  the  same  pulse-rate  as  the 
last  period  with  the  clinical  chamber. 


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On  February  15-16,  the  average  pulse-rate  before  injection  was  62  beats 
per  minute.  In  the  course  of  2  hours  after  injection  the  rate  rose  to  70  beats 
and  remained  at  practically  this  level  throughout  the  night.  In  the  observa¬ 
tions  with  the  gasometer  and  mask  combination  in  the  morning,  with  the 
subject  awake,  the  average  pulse-rate  was  76  beats. 

On  March  2-3,  there  were  no  periods  with  the  clinical  respiration  chamber 


RESPIRATARY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  125 


preliminary  to  the  injection,  although  7  periods  with  the  mask  and  gasometer 
preceded  it.  The  pulse-rate  in  the  gasometer  and  mask  experiments  was 
about  63  beats  per  minute,  and  was  practically  the  same  in  the  chamber 
experiment  in  the  first  2  hours  after  injection.  It  rose  thereafter  for  a  short 
time  to  73  beats,  then  dropped  to  a  level  of  65  beats,  until  during  the  seventh 
and  eighth  hours  after  injection  when  it  averaged  about  70  beats.  In  the 


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supplementary  experiments  in  the  morning  with  the  mask  and  gasometer  and 
the  subject  awake,  the  pulse-rate  averaged  69  beats. 

On  March  23-24,  in  the  periods  with  the  mask  and  gasometer  when  the 
subject  was  asleep  and  before  injection  took  place,  the  average  pulse-rate 
was  67  beats  and  continued  at  about  this  level  during  the  periods  in  the 
chamber  before  injection.  Within  2  hours  after  the  injection  the  pulse-rate 


126 


HUMAN  METABOLISM  WITH  ENEMATA. 


rose  from  a  level  of  66  beats  to  80  beats,  and  remained  between  80  and  75 
beats  much  of  the  entire  night  until  the  last  two  periods  in  the  morning,  when 
it  rose  to  82  and  87  beats.  In  the  morning  periods  with  the  mask  and  gasom¬ 
eter,  and  with  the  subject  awake,  the  pulse-rate  was  on  the  same  level  as 
during  the  last  period  in  the  chamber. 

This  marked  effect  upon  the  pulse-rate  after  alcohol  injection  is  therefore  a 
positive  one  and  confirms  the  changes  in  pulse-rate  which  were  obtained  in 
the  experiments  with  the  mask  and  gasometer  combination. 

Oxygen  absorption  and  carbon-dioxide  elimination. — The  oxygen  absorp¬ 
tion  after  the  injection  of  500  c.  c.  of  a  7.5  per  cent  alcohol  solution  by  rectum 
was  increased  in  the  course  of  5  or  6  hours  in  some  cases  as  much  as  20 
per  cent.  This  change  was  very  gradual  but  was  positive  in  practically  all 
of  the  experiments.  The  increase  is  somewhat  confirmed  by  a  more  gradual 
rise  in  the  carbon-dioxide  elimination. 

Respiratory  quotient. — The  respiratory  quotient  in  the  five  chamber  ex¬ 
periments  was  lowered  as  a  result  of  the  injection  of  a  7.5  per  cent  solution 
of  alcohol,  this  fall  amounting  at  times  to  as  much  as  0.05  and  0.07  in  the 
course  of  3  or  4  hours.  The  lowest  level  appeared  to  be  reached  about  5  to 
6  hours  after  the  injection  began,  with  an  indication  of  a  rise  at  the  end  of 
the  fifth  and  sixth  hours.  In  these  experiments  the  effect  is  absolutely  clear 
in  contrast  to  the  results  obtained  with  the  7.5  per  cent  solution  in  experi¬ 
ments  with  the  gasometer  apparatus  and  short  periods.  As  the  subject 
was  asleep  practically  the  whole  period  of  observation  in  the  chamber 
experiments,  the  results  of  the  alcohol  injection  were  not  obscured  by  changes 
from  sleep  to  waking.  In  the  experiments  with  the  clinical  chamber  (see 
p.  102),  in  2  of  which  sodium  chloride  was  injected,  there  was  a  very  slight 
(0.03)  increase  in  the  respiratory  quotient  during  the  night.  With  the  7.5 
per  cent  alcohol  solution  there  was  a  depression  of  the  respiratory  quotient. 
This  depression  corresponds  to  the  theoretical  effect  of  the  utilization  of 
alcohol  in  metabolism,  namely,  a  lowering  of  the  respiratory  quotient.  The 
effects  of  the  injection  of  alcohol  in  these  experiments  in  depressing  the 
respiratory  quotient  are  therefore  clearly  defined. 

Discussion  of  Composite  Chart  of  Chamber  Experiments. 

A  composite  chart  has  been  drawn  of  the  results  of  the  five  experiments  in 
which  500  c.  c.  of  a  7.5  per  cent  alcohol  solution  were  injected  rectally  while 
subject  A  was  in  the  chamber  respiration  apparatus.  (See  fig.  55.)  The 
averages  are  drawn  for  an  hour  before  injection  and  for  6|  hours  after  the 
injection  began  and  give  results  for  the  respiratory  quotient,  oxygen  ab¬ 
sorption,  and  pulse-rate  per  minute. 

Pulse-rate. — The  pulse-rate  during  the  first  hour  before  injection  was  be¬ 
tween  61  and  62  beats.  It  rose  gradually  after  injection  and  for  2  hours  there 
was  a  steady  rise,  the  average  value  at  the  end  of  2  hours  being  about  68 
beats.  Subsequently  it  rose  steadily,  but  at  a  much  slower  rate  for  the  next 
3  hours,  reaching  at  the  end  of  that  time  70  beats  per  minute.  When  the 
observations  were  concluded  6J  hours  after  the  beginning  of  the  injection, 
the  pulse-rate  was  still  rising,  with  an  average  of  about  73  beats  per  minute. 
There  was,  therefore,  on  the  average,  a  steady  rise  in  the  pulse-rate  after 
the  injection  of  500  c.  c.  of  a  7.5  per  cent  alcohol  solution. 

Oxygen  absorption. — The  oxygen  absorption  during  the  preliminary  hour 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  127 


averaged  about  185  c.  c.  Then  1  hour  after  injection  began  it  rose  to  200 
c.  c.  per  minute.  From  then  on  throughout  the  rest  of  the  6|  hours  after 
injection  there  was  a  slow  and  gradual  rise.  At  the  end  of  6J  hours  there  was 
a  value  of  about  225  c.  c.  so  that  there  was  a  rise  of  40  c.  c.  per  minute  in  the 
oxygen  absorption  due  to  the  ingestion  of  500  c.  c.  of  a  7.5  per  cent  alcohol 
solution. 

Respiratory  quotient. — The  average  respiratory  quotient  for  the  hour  before 
injection  began  was  somewhat  high  for  this  particular  subject,  being  0.84. 
The  respiratory  quotient  after  the  first  half  hour  fell  markedly,  and  at  the 
end  of  the  second  hour  had  reached  0.78,  at  which  point  it  remained  for  the 
rest  of  the  experimental  period.  There  was  therefore  a  total  fall  of  0.06  due 
to  the  injection  of  500  c.  c.  of  a  7.5  per  cent  alcohol  solution. 


Fig.  55. — Chart  showing  composite  results  for  measurements  of  respiratory  quotient,  oxygen 
absorption,  and  pulse-rate  in  5  experiments  with  rectal  injection  of  37.5  grams  of  alcohol  in  a 
7.5  per  cent  solution.  (Clinical  respiration  chamber.) 


As  a  whole,  therefore,  the  composite  chart  shows  definite  changes  due  to 
the  injection  of  37.5  grams  of  alcohol  in  the  form  of  a  7.5  per  cent  alcohol 
solution.  These  changes  are  a  marked  increase  in  the  pulse-rate,  a  lower 
respiratory  quotient,  and  a  marked  increase  in  oxygen  absorption. 

GENERAL  SUMMARY  OF  RESULTS  WITH  A  7.5  PER  CENT  ALCOHOL  SOLUTION- 

Both  groups  of  experiments,  namely,  those  with  the  mask  and  gasometer 
and  those  with  the  clinical  respiration  chamber,  indicate  that  a  7.5  per  cent 
alcohol  solution  in  quantities  varying  from  250  c.  c.  to  500  c.  c.  increases 
markedly  the  pulse-rate  and  lowers  the  respiratory  quotient.  This  effect 
continues  for  a  period  as  long  as  6  or  7  hours  in  some  experiments  and  begins 
as  early  as  1  hour  after  the  beginning  of  the  injection.  When  the  quantity  is 
as  large  as  500  c.  c.,  the  oxygen  absorption  is  increased  nearly  20  per  cent, 
indicating  both  a  utilization  of  alcohol  by  the  subject  and  a  stimulating  in¬ 
fluence  of  alcohol  upon  the  total  metabolism. 


128 


HUMAN  METABOLISM  WITH  ENEMATA. 


Experiments  with  a  10  per  cent  Alcohol  Solution. 

Four  experiments  with  260  to  265  c.  c.  of  a  10  per  cent  alcohol  solution  in¬ 
troduced  rectally  were  made  with  three  subjects,  A,  C,  and  D.  The  general 
details  of  the  observations  are  given  in  table  25.  The  duration  of  injection 
was  recorded  in  but  three  experiments,  with  variation  between  1  minute  and 
26  minutes.  The  number  of  periods  before  injection  ranged  between  3  and  6, 
and  the  time  covered  from  30  minutes  to  1  hour.  The  periods  after  the  be¬ 
ginning  of  the  injection  varied  in  number  from  14  to  21,  and  in  the  duration 
of  observation  after  alcohol  from  2  hours  and  20  minutes  to  3  hours  and  40 
minutes.  The  gasometer  and  mask  apparatus  and  the  sleep  recorder  were 
used  in  all  of  the  experiments.  The  statistics  of  the  experiments  are  given  in 
table  25  and  the  results  graphically  recorded  in  figures  56  to  59.  The  condi¬ 
tions  of  these  experiments  were  the  same  as  in  the  previous  group.  All  four 
experiments  were  made  in  the  latter  part  of  the  afternoon  and  early  evening. 
The  last  meal  was  in  all  cases  between  lh  15m  and  2  p.m.,  and  in  three  of  the 
four  experiments  the  beginning  of  the  first  period  was  less  than  a  half-hour 
after  the  subject  lay  down. 


Table  25. — Statistics  of  respiratory  exchange  observations  before  and  after  the  injection  by 

rectum  of  a  10  per  cent  alcohol  solution. 


Subject. 

Date.0 

Alcohol  injected. 

Duration 

of 

injection. 

Periods  before 
injection. 

Periods  after 
injection. 

Volume 

of 

solution. 

Weight 

of 

alcohol. 

No. 

Time 

covered. 

No. 

Time 

covered. 

1916. 

c.  c. 

gm. 

min. 

h.  min. 

h.  min. 

A 

Mar.  6 

265 

26.5 

23 

5 

0  50 

21 

3  30 

Mar.  24 

260 

26.0 

#  . 

6 

1  00 

14 

2  20 

C 

Mar.  8 

265 

26.5 

1 

3 

0  30 

16 

3  00 

D 

Mar.  10 

265 

26.5 

26 

5 

0  50 

20 

3  40 

°  The  gasometer  and  mask  method,  with  the  subject  in  the  lying  position,  was  used  in  all  of  these 
experiments. 


RESULTS  OF  MEASUREMENTS  BEFORE  RECTAL  INJECTION. 

Pulse-Rate. 

The  average  pulse-rate  in  the  periods  before  injection  with  subject  A  was 
70  beats  on  March  6  and  64  beats  on  March  24.  The  pulse-rate  on  March  6 
was  rather  high  for  an  average  and  the  value  for  the  preliminary  oxygen  ab¬ 
sorption  was  also  high.  The  last  meal  on  this  day  was  at  2  o’clock,  about 
3i  hours  before  the  experiment  began,  and  was  fairly  abundant.  The  fact 
that  the  respiratory  quotient  was  not  high  and  did  not  fall  gradually  indi¬ 
cates  that  the  high  metabolism  was  not  due  to  the  influence  of  a  previous 
mixed  meal.  If  the  preceding  meal  had  contained  a  large  amount  of  protein, 
it  would  account  for  the  increased  oxygen  consumption,  but  the  subject’s 
report  gave  no  evidence  of  this.  Consequently,  it  is  difficult  to  explain  why 
the  metabolism  of  the  subject  was  so  high  at  this  period  of  the  day.  The 
preliminary  pulse-rate  for  D  was  78  beats  per  minute  and  the  average  for  C 
was  65  beats,  which  is  close  to  his  basal  pulse-rate. 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  129 


Oxygen  Absorption. 

As  pointed  out  in  the  paragraph  above,  the  average  oxygen  absorption 
with  A  before  injection  on  March  6  was  high,  242  c.  c.  This  high  metabolism 
is  not  easy  to  explain.  As  already  noted,  the  pulse-rate  at  the  beginning  of 
the  experiment  was  higher  than  usual.  The  oxygen  absorption  in  the  ex¬ 
periment  of  March  24  was  209  c.  c.  which  is  near  the  average  basal  oxygen 
absorption  for  this  subject.  The  average  absorption  for  C  on  March  8  was 
266  c.  c.  in  the  periods  before  injection;  for  D  (March  10)  it  was  226  c.  c. 
These  figures  are  near  the  average  preliminary  values  which  have  previously 
been  discussed. 

Respiratory  Quotient. 

The  preliminary  respiratory  quotients  in  the  two  experiments  with  subject 
A  were  0.81  and  0.77,  respectively;  for  C  on  March  8,  0.82,  and  for  D,  0.83. 
The  respiratory  quotients  before  injection  were  therefore  all  normal  for  the 
conditions  under  which  these  experiments  were  carried  out. 


SUBJECT  A.  MAR.  6.  1916 


56 


SUBJECT  A.  MAR.  24,  1916 

260  c.  c.  10  PER  CENT .ALCOHOL  MASK 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 

57 


Fig.  56. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  March  6,  1916, 
before  and  after  rectal  injection  of  265  c.  c.  of  a  10  per  cent  alcohol  solution.  (Mask,  with 
continuous  observation.) 

The  horizontal  line  at  the  bottom  of  this  and  subsequent  charts  gives  a  record  of  sleep,  the 
solid  portions  indicating  when  the  subject  was  asleep  and  the  broken  portions  when  he  was 
awake. 

Fig.  57. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  March  24,  1916, 
before  and  after  the  rectal  injection  of  260  c.  c.  of  a  10  per  cent  alcohol  solution.  (Mask,  with 
continuous  observation.) 


RESULTS  OF  MEASUREMENTS  AFTER  RECTAL  INJECTION  OF  A  10  PER  CENT 

ALCOHOL  SOLUTION. 

Two  of  the  experiments  with  a  10  per  cent  alcohol  solution  were  made  with 
subject  A.  In  his  first  experiment  the  subject  was  asleep  during  the  entire 
period,  with  slight  restlessness  at  the  first.  Within  the  first  hour  after  the 
beginning  of  the  alcohol  injection  there  was  a  marked  fall  in  the  respiratory 
quotient  from  a  general  level  of  0.81  to  0.75,  the  lower  level  continuing  for  the 
rest  of  the  experiment.  In  the  second  experiment  with  the  same  subject 
(March  24),  there  was  an  interruption  in  the  values  immediately  after  the 
giving  of  alcohol,  with  a  sharp  decline  in  the  respiratory  quotient  in  the  first 


130 


HUMAN  METABOLISM  WITH  ENEMATA. 


half  hour.  However,  the  quotient  rose  again,  so  that  if  the  first  hour  after 
the  injection  were  omitted,  there  would  be  practically  no  significant  variation 
in  the  respiratory  quotient  during  the  whole  experiment.  The  oxygen  ab¬ 
sorption  was  apparently  not  affected  in  the  experiment  on  March  6,  since  it 
did  not  increase,  though  there  was  a  very  gradual  but  slight  descent.  In  the 
experiment  on  March  24,  also,  it  was  not  affected.  The  pulse-rate  in  the 
experiment  on  March  6  was  hardly,  if  any,  influenced  by  the  alcohol,  while  in 
the  experiment  of  March  24  it  was  raised  slightly. 


SUBJECT  C,  MAR.  8.  1916 

265  c.  c.  10  PER  CENT  ALCOHOL  MASK 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


Fig.  58. — Respiratory  quotient,  oxygen  absorp¬ 
tion,  and  pulse-rate  of  subject  C,  March 
8,  1916,  before  and  after  rectal  injection  of 
265  c.  c.  of  a  10  per  cent  alcohol  solution. 
(Mask,  with  continuous  observation.) 


The  experiment  with  C  (March  8)  was  fortunately  uncomplicated  by  sleep, 
as  the  subject  was  awake  the  entire  time.  Within  the  first  hour  after  the 
alcohol  was  given  there  was  a  decided  fall  in  the  respiratory  quotient  from  an 
average  of  0.82  until  it  reached  0.77  in  the  second  hour.  The  pulse-rate  rose 
materially,  i.  e.,  about  5  beats,  but  part  of  this  increase  was  due  to  a  desire  to 
urinate,  though  the  high  level  continued,  with  some  variation,  even  after 
urination.  The  oxygen  absorption  was  little  affected  by  the  alcohol  injec¬ 
tion,  its  subsequent  course  being  even. 


Fig.  59. — Respiratory  quotient,  oxy¬ 
gen  absorption,  and  pulse-rate 
of  subject  D,  March  10,  1916, 
before  and  after  the  rectal  in¬ 
jection  of  265  c.  c.  of  a  10  per 
cent  alcohol  solution.  (Mask, 
with  continuous  observation.) 


SUBJECT  D,  MAR.  10. 1916 

265  c.  c.  10  PER  CENT  ALCOHOL  MASK 


In  the  experiment  with  subject  D,  the  respiratory  quotient  fell  to  0.75 
within  the  first  hour  after  the  injection  of  the  alcohol  and  continued  near 
this  point  up  to  the  last  period  before  the  interruption,  when  it  rose  again 
to  about  the  preliminary  level.  After  the  intermission  it  returned  to  ap- 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  131 


proximately  the  average  lower  level,  even  though  the  subject  was  awake. 
This  experiment  is  partly  complicated  by  sleep,  but  the  influence  of  the  al¬ 
cohol  does  not  seem  to  be  obscured  by  this  factor.  The  oxygen  absorption 
was  not  affected  to  any  great  extent.  The  pulse-rate  was  definitely  lower 
immediately  after  the  injection  and  was  then  slightly  raised;  during  the  last 
hour  of  the  experiment  it  was  materially  higher  than  in  the  period  immedi¬ 
ately  following  the  giving  of  the  alcohol. 

The  injection  of  265  c.  c.  of  a  10  per  cent  alcohol  solution  produced  in  three 
of  four  experiments  a  notable  fall  in  the  respiratory  quotient.  In  two  ex¬ 
periments  there  was  a  positive  increase  in  the  pulse-rate,  but  none  of  the 
observations  gave  evidence  of  a  definite  rise  in  the  oxygen  absorption.  The 
effect  of  these  injections  of  a  10  per  cent  solution  is,  however,  more  marked 
than  the  effect  of  the  5  per  cent  solution  containing  about  the  same  amount 
of  alcohol.  (See  p.  111.) 

DISCUSSION  OF  COMPOSITE  CHART  OF  EXPERIMENTS  WITH  A  10  PER  CENT 

ALCOHOL  SOLUTION. 

A  composite  chart  of  the  results  of  the  four  experiments  with  a  10  per  cent 
alcohol  solution  is  given  in  figure  60. 


Fig.  60. — Chart  showing  composite 
results  for  measurements  of 
respiratory  quotient,  oxygen 
absorption,  and  pulse-rate  in  4 
experiments  with  rectal  injec¬ 
tion  of  26  to  26.5  grams  of  al¬ 
cohol  in  a  10  per  cent  solution. 
(Mask.) 


COMPOSITE  CHART 

RECTAL  INJECTION  OF  10  PER  CENT  ALCOHOL  SOLUTION 


0.80 

0.75 

0.70 

275 

250 

225 

200 

80 

75 

70 

65 

RESPIRA 

TORY  o' 

UOTIEN 

r 

( 

J2  PER  l\ 

1INUTE, 

c.  c. 

■’ULSE  F 

ER  MIN 

JTE 

C) 

1 

2  3  < 

5  6  7 

HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


Pulse-rate. — The  pulse-rate  shows  no  very  definite  change  until  about  2\ 
hours  after  the  injection.  Thereafter  until  the  end  of  the  experiment  (about 
4  hours  after  the  injection  began)  there  was  a  slight  rise. 

Oxygen  absorption. — During  the  preliminary  period  the  oxygen  absorption 
was  about  235  c.  c.  Beginning  with  the  third  half  hour  after  injection,  there 
was  a  steady  rise,  so  that  at  the  end  of  the  experiment  the  average  value  was 
250  c.  c. 

Respiratory  quotient. — The  respiratory  quotient  fell  very  slightly  from  the 
preliminary  45  minutes  until  the  second  hour  after  injection,  but  had  a 
tendency  to  rise  towards  the  end  of  the  experiment. 

This  chart  is  the  least  definite  of  all  the  composite  charts  in  its  indications 
of  the  effect  of  alcohol  injection.  The  explanation  for  this  difference  may  be 
found  in  the  small  number  of  experiments  in  the  series  and  the  relatively 


132 


HUMAN  METABOLISM  WITH  ENEMATA. 


large  amount  of  sleep  which  in  one  experiment  (March  6)  may  have  exerted 
an  unusually  depressing  influence  on  the  metabolism,  and  in  another 
(March  10)  caused  considerable  variation  in  the  results  because  of  the 
alternate  sleeping  and  waking.  The  tendency  is  toward  a  balanced  effect 
upon  the  changes  already  noted  as  occurring  in  the  course  of  the  experi¬ 
ments  and  the  composite  does  not  have  the  distinctive  features  of  the 
alcohol  effect  apparent  in  the  individual  experiments. 

RESPIRATORY  EXCHANGE  AS  INFLUENCED  BY  ALCOHOL 

GIVEN  BY  MOUTH. 

With  two  of  the  subjects,  A  and  C,  a  few  experiments  were  made  in  which 
alcohol  was  given  by  mouth,  and  the  three  concentrations  employed  which 
were  used  in  the  rectal  injections,  i.  e.,  5,  7.5,  and  10  per  cent.  A  number  of 
observations  of  the  respiratory  exchange  after  alcohol  taken  by  mouth  have 
been  made  by  Higgins 1  and  published  in  an  earlier  communication  from  this 
Laboratory,  together  with  a  review  of  the  previous  literature  on  the  influence 
of  alcohol  upon  the  respiratory  exchange.  Higgins  gave  30  c.  c.  and  45  c.  c. 
(24  and  36  grams)  of  alcohol  in  200  c.  c.  of  cereal  coffee  infusion;  25  c.  c.  of 
water  were  given  afterwards.  His  measurements  of  the  respiratory  ex¬ 
change  were  made  upon  7  subjects,  breathing  through  the  mouthpiece,  the 
short-period  observations  continuing  from  2  to  3  hours  at  intervals  after  the 
alcohol  and  control  solutions  had  been  given.  He  found  that  in  about  one- 
fifth  of  the  experiments  there  was  a  rise  of  5  to  7  per  cent  in  the  oxygen  ab¬ 
sorption.  In  about  45  per  cent  of  the  experiments  there  was  a  relative 
acceleration  of  the  pulse-rate.  Calculations  made  by  Higgins  from  the 
respiratory  quotient  indicated  that  45  c.  c.  did  not  burn  more  rapidly  than 
30  c.  c.  and  that  20  to  40  per  cent  of  the  metabolism  was  due  to  alcohol. 

Miles2  measured  the  oxygen  consumption  with  the  Benedict  portable  ap¬ 
paratus  and  also  the  pulse-rate  approximately  2J  to  3  hours  after  27.5 
grams  of  alcohol  had  been  taken  by  mouth  in  1,000  c.  c.  of  water,  alcohol-free 
beer,  or  grape-juice.  Two  successive  measurements  of  15  minutes’  duration 
each  were  made,  with  the  subject  in  the  sitting  position.  In  three  experi¬ 
ments  with  water  alone  the  average  oxygen  consumption  for  the  two  periods 
was  242  and  244  c.  c.  per  minute,  and  the  pulse-rate  65  and  68  beats  per 
minute,  respectively.  With  alcohol  and  water  the  oxygen  consumption  was 
255  and  261  c.  c.  per  minute  and  the  pulse-rate  was  72  and  73  beats  per 
minute.  When  the  alcohol-free  beer  was  used,  the  control  values  for  oxygen 
were  235  and  242  c.  c.,  with  the  pulse-rate  65  and  66  beats.  When  27.5 
grams  of  alcohol  were  added  to  the  beer,  the  oxygen  values  were  249  c.  c.  and 
the  pulse-rates  69  beats  for  both  periods.  With  grape-juice  as  a  control,  the 
oxygen  values  were  244  c.  c.  and  254  c.  c.  and  the  pulse-rate  64  and  66  beats, 
respectively.  When  27.5  grams  of  alcohol  were  added,  the  oxygen  values 
changed  to  253  and  255  c.  c.,  and  the  pulse-rates  to  66  and  70  beats.  Thus 
there  was  an  increase  in  oxygen  consumption  and  pulse-rate  in  all  three 
groups  of  experiments,  the  most  marked  being  when  the  alcohol  was  taken  in 
water  alone. 

The  quantity  of  alcohol  in  the  Miles  experiments  was  slightly  larger  than 


1  Higgins:  Journ.  Pharm.  and  Exp.  Therapeutics,  1917,  9,  p.  441. 

*  Miles:  Carnegie  Inst.  Wash.  Pub.  No.  333,  1924,  pp.  177-180. 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  133 


that  used  for  most  of  the  experiments  reported  in  this  monograph,  but  the 
dilution  was  greater.  Furthermore,  while  Higgins  used  cereal  coffee  and 
Miles  employed  water,  alcohol-free  beer,  or  grape-juice  to  dilute  the  alcohol, 
in  the  series  of  experiments  discussed  in  this  section  the  alcohol,  when  given 
by  mouth,  was  diluted  with  water  only  and  the  respiratory  exchange  was 
measured  continuously  in  short  periods  by  use  of  the  mask,  as  in  many  of  the 
experiments  with  rectal  feeding.  According  to  the  ordinary  routine,  pre¬ 
liminary  observations  were  made  for  about  an  hour.  The  mask  was  then 
removed,  the  subject  drank  the  solution  of  alcohol  and  water  as  quickly  as 
possible,  the  mask  was  again  adjusted,  and  the  measurements  were  con¬ 
tinued.  In  one  case  the  mask  was  not  removed,  but  the  subject  took  the 
alcohol  solution  through  a  tube  inserted  in  the  mask. 


Table  26. — Statistics  of  respiratory  exchange  observations  before  and  after  the  ingestion  by 
mouth  of  5  per  cent,  7.5  per  cent ,  and  10  per  cent  alcohol  solutions. 


Volume  of 

Periods  before 

Periods  after 

solution 

Weight 

Time 

alcohol. 

alcohol. 

Subject. 

Date.0 

and 

of 

of 

concentra- 

alcohol. 

drinking. 

No. 

Time 

No. 

Time 

tion. 

covered. 

covered. 

1915. 

c.  c. 

5  p.  ct. 

grams. 

min. 

h.  min. 

h.  min. 

C 

Dec.  15 

400 

20 

3 

6 

1  00 

24 

3  1 

A 

Dec.  17 

400 

20 

6 

6 

1  00 

21 

2  53 

C 

Dec.  23 

400 

20 

3 

5 

0  49 

20 

2  48 

1916. 

7.5  p.  ct. 

A 

Mar.  27 

250 

18.8 

1 

6 

1  00 

25 

3  30 

C 

Apr.  1 

250 

10  p.  ct. 

18.8 

1 

0 

0  00 

36 

5  30 

A 

Apr.  20 

250 

25 

4 

5 

0  59 

26 

5  55 

°  The  gasometer  and  mask  method,  with  the  subject  in  the  lying  position,  was  used  in  all  of  these 
experiments. 


Table  26  gives  information  regarding  the  details  of  these  observations. 
Three  experiments  were  made  with  400  c.  c.  of  a  5  per  cent  alcohol  solution, 
the  subjects  requiring  from  3  to  6  minutes  to  drink  this  quantity.  The  num¬ 
ber  of  periods  preliminary  to  the  alcohol  ingestion  ranged  from  5  to  6  and  the 
time  covered  was  from  49  minutes  to  1  hour.  The  number  of  alcohol  periods 
varied  from  20  to  24  and  the  minimum  and  maximum  times  were  2  hours  and 
48  minutes  and  3  hours  and  1  minute. 

Two  experiments  were  made  with  250  c.  c.  of  a  7.5  per  cent  alcohol  solu¬ 
tion.  In  one  of  these  there  was  no  preliminary  period,  but  the  measurements 
were  made  immediately  after  the  alcohol  was  taken,  so  that  the  effect  might 
be  observed  over  as  long  a  period  as  possible.  In  this  case  the  experiment 
continued  5  hours  and  30  minutes  after  the  alcohol  was  given.  One  experi¬ 
ment  was  also  made  in  which  250  c.  c.  of  a  10  per  cent  alcohol  solution  was 
taken  by  the  subject,  this  containing  25  grams  of  alcohol.  The  preliminary 
period  extended  over  59  minutes,  divided  into  5  periods;  the  number  of 
alcohol  periods  was  26  and  the  time  covered  about  6  hours.  The  results  of 
the  experiments  on  the  measurements  of  respiratory  exchange  after  alcohol 
given  by  mouth  are  presented  in  the  form  of  curves  (figs.  61  to  66),  as  in  the 
preceding  sections.  The  detailed  discussion  of  the  observations  follows. 


134 


HUMAN  METABOLISM  WITH  ENEMATA. 


Results  of  Measurements  Before  Alcohol  was  Taken. 

The  experiments  with  alcohol  given  by  mouth  were  conducted  under  the 
same  conditions  as  the  experiments  with  rectal  injection,  that  is,  the  sub¬ 
jects  came  to  the  Laboratory  in  the  early  evening  or  late  afternoon.  The 
latest  time  at  which  food  was  taken  before  the  observations  was  at  lh  30m 


SUBJECT  C.  DEC.  15,  1915 

400  c.c.  5  PER  CENT  ALCOHOL  BY  MOUTH  MASK 


Fig.  61. — Respiratory  quotient,  oxygen 
absorption,  and  pulse-rate  of  subject 
C,  December  15,  1915,  before  and 
after  ingestion  by  mouth  of  400  c.  c. 
of  a  5  per  cent  alcohol  solution. 
(Mask,  with  continuous  observa¬ 
tion.) 


p.  m.  The  experiment  with  subject  A  on  April  20  was  made  in  the  morning 
and  was  preceded  by  a  very  light  breakfast.  The  results  of  the  pre-injection 
periods  for  this  experiment  indicate  a  slightly  high  carbohydrate  metabolism. 
The  oxygen  absorption,  however,  averaged  only  189  c.  c.  for  the  three 
periods  before  the  injection  and  was  therefore  near  the  average  normal  basal 
for  this  individual  (206  c.  c.). 


0.90 

0.85 

0.80 

Fig.  62. — Respiratory  quotient,  oxygen  ab¬ 
sorption,  and  pulse-rate  of  subject  A,  0  75 
December  17,  1915,  before  and  after  225 
ingestion  by  mouth  of  400  c.  c.  of  a  5 
per  cent  alcohol  solution.  (Mask,  with  2oo 
continuous  observation.) 

175 

65 

60 


HALF  HOURS  AFTER  INGESTION  BY  MOUTH 


SUBJECT  A.  DEC.  17.  1915 

400  c.c.  5  PER  CENT  ALCOHOL  BY  MOUTH  MASK 


Pulse-Rate. 

The  average  pulse-rate  in  the  preliminary  periods  of  the  experiments  with 
A  varied  from  60  beats  on  December  17  to  68  beats  on  March  27;  the  latter 
pulse-rate  was  somewhat  high  for  this  individual.  The  oxygen  absorption, 
223  c.  c.,  was  also  high,  with  a  respiratory  quotient  of  0.85.  The  last  meal, 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  135 


however,  was  at  lh  30m  p.  m.  and  the  first  period  recorded  on  the  chart  began 
at  4h  49m  p.  m.  The  preliminary  pulse-rates  of  C  on  December  15  and  Decem¬ 
ber  23  were  72  and  62  beats  per  minute,  respectively.  There  were  no 
preliminary  periods  on  April  1. 


Fig.  63. — Respiratory  quotient,  oxygen 
absorption,  and  pulse-rate  of  sub¬ 
ject  C,  December  23,  1915,  before 
and  after  ingestion  by  mouth  of 
400  c.  c.  of  a  5  per  cent  alcohol  solu¬ 
tion.  (Mask,  with  continuous  ob¬ 
servation.) 


SUBJECT  C.  DEC.  23.  1915 

400  c.  c.  5  PER  CENT  ALCOHOL  BY  MOUTH  MASK 


Oxygen  Absorption. 

The  oxygen  absorption  in  the  preliminary  periods  with  A  varied  from  189 
on  April  20  to  223  c.  c.  on  March  27,  the  value  in  the  third  experiment  being 
197  c.  c.  per  minute.  The  average  of  the  oxygen-absorption  values  for  the 
preliminary  periods  recorded  on  the  chart  for  C  on  December  15  is  314  c.c., 
a  very  high  value  for  the  oxygen  absorption  of  this  subject,  the  average 


SUBJECT  A.  MAR.  27  1916 

250  c.  c.  7.5  PER  CENT  ALCOHOL  BY  MOUTH  MASK 


Fig.  64. — Respiratory  quotient,  oxy¬ 
gen  absorption,  and  pulse-rate 
of  subject  A,  March  27,  1916, 
before  and  after  ingestion  by 
mouth  of  250  c.  c.  of  a  7.5  per 
cent  alcohol  solution.  (Mask, 
with  continuous  observation.) 


preliminary  value  for  the  experiment  on  December  23  being  only  263  c.  c. 
The  last  meal  on  December  15  was  at  7h  45m  a.  m.  and  the  first  period  was 
at  6h  03m  p.  m.;  consequently  this  high  value  can  not  be  due  to  the  influence 
of  food.  The  respiratory  quotient  on  that  day  was  0.78. 


136 


HUMAN  METABOLISM  WITH  ENEMATA. 


Respiratory  Quotient. 

The  preliminary  respiratory  quotients  for  A  varied  from  0.80  to  0.86; 
the  respiratory  quotients  for  C  in  two  experiments  were  0.78  and  0.80. 
The  preliminary  respiratory  quotients  in  this  series  of  mouth  experiments, 
except  in  the  experiments  with  A  on  March  27  and  April  20,  are  very  near 
the  normal  post-absorptive  values. 

Results  of  Measurements  After  Alcohol  was  Taken. 

In  three  experiments  with  400  c.  c.  of  a  5  per  cent  alcohol  solution,  one  was 
with  subject  A  and  the  other  two  with  subject  C.  In  the  experiment  with 
subject  A  on  December  17  (fig.  62),  the  respiratory  quotient  fell  about  0.05 
within  the  first  20  minutes  of  the  giving  of  the  alcohol.  After  an  hour  and  a 
half  it  rose  to  a  level  slightly  higher,  but  did  not  reach  the  level  for  the  pre¬ 
liminary  period.  The  oxygen  absorption  was  not  materially  altered  by  the 
ingestion  of  this  amount  of  alcohol,  falling  slightly,  if  anything,  during  the 
subsequent  second  or  third  hour.  The  course  of  the  pulse-rate  was  varying 
and  showed  no  change  of  direction  which  could  be  attributed  to  the  influence 
of  alcohol. 


SUBJECT  C. APR.  1.  1916 

250  c.  c.  7.5  PER  CENT  ALCOHOL  BY  MOUTH  MASK 


Fig.  65. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  sub¬ 
ject  C,  April  1,  1916,  after  ingestion  by  mouth  of  250  c.  c.  of  a  7.5 
per  cent  alcohol  solution.  (Mask,  with  continuous  observation.) 

The  horizontal  line  at  the  bottom  of  this  and  subsequent  charts 
gives  a  record  of  sleep,  the  solid  portions  indicating  when  the  sub¬ 
ject  was  asleep,  and  the  broken  portions  when  he  was  awake. 

In  the  experiment  with  subject  C  on  December  15  (fig.  61)  there  was  a 
slight  fall  (0.02  on  the  average)  in  the  second  hour  in  the  respiratory  quo¬ 
tient.  The  pulse-rate  fell  somewhat  during  the  experiment  and  there  was 
likewise  a  reduction  in  the  oxygen  consumption,  but  apparently  these 
changes  were  not  due  to  the  alcohol.  In  the  experiment  on  December  23 
with  the  same  man  (see  fig.  63)  there  was  very  little  change  in  the  respiratory 
quotient  in  the  first  hour  after  the  alcohol  was  taken,  but  in  the  third  hour 
the  average  respiratory  quotient  was  somewhat  lower  (0.03)  than  that 
during  the  preliminary  period.  The  pulse-rate  was  not  affected  by  the 
alcohol.  The  oxygen  absorption  was  slightly  higher  in  the  three  half  hours 
immediately  following  the  giving  of  the  alcohol. 

The  ingestion  of  400  c.  c.  of  a  5  per  cent  alcohol  solution  by  mouth  thus 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  137 

lowered  the  respiratory  quotient  (0.02  to  0.03)  in  three  experiments.  The 
oxygen  consumption  and  heart-rate  were  not  affected. 

Two  experiments  were  made  with  subjects  A  and  C  in  which  250  c.  c.  of  a 
7.5  per  cent  alcohol  solution  were  given.  In  the  experiment  with  subject  A 
(fig.  64)  there  was  an  immediate  lowering  of  the  respiratory  quotient,  and  it 
remained  at  this  lower  level  (about  0.79)  until  the  third  hour,  when  a  still 
lower  average  respiratory  quotient  was  found  (0.77).  The  pulse-rate  did 
not  change  until  the  last  hour  of  the  experiment,  when  it  rose  slightly,  and 
the  oxygen  absorption  was  not  affected.  In  the  experiment  with  subject  C 
(fig.  65)  an  immediate  fall  was  found  in  the  respiratory  quotient  following 
the  alcohol,  as  in  the  experiment  with  A.  Since  there  were  no  preliminary 
periods,  it  can  not  be  stated  definitely  whether  this  fall  was  due  to  the  taking 
of  the  alcohol  or  to  activity  preceding  its  ingestion.  The  general  course  of 
the  quotient  did  not  seem  to  change  materially  throughout  the  rest  of  the 
experiment,  except  that  it  tended  to  rise  in  the  last  hour  and  a  half,  5  or  6 
hours  after  the  taking  of  the  alcohol.  Both  the  oxygen  consumption  and 
pulse-rate  rose  2  or  3  hours  after  the  alcohol  was  taken. 

SUBJECT  A.  APR.  20.  1916 


Fig.  66. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  April 
20,  1916,  before  and  after  ingestion  by  mouth  of  250  c.  c.  of  a  10  per  cent  alcohol 
solution.  (Mask,  with  continuous  observation.) 


In  one  experiment  with  subject  A,  250  c.  c.  of  a  10  per  cent  solution  of 
alcohol  was  given.  (See  fig  66.)  The  ingestion  was  followed  immediately 
by  a  definite  lowering  of  the  respiratory  quotient  from  0.85  to  0.80.  The 
general  level  of  the  oxygen  absorption  was  about  10  per  cent  higher  after 
the  alcohol,  though  the  effect  was  somewhat  delayed.  The  pulse-rate  varied 
in  its  course,  being  somewhat  higher  in  the  hour  after  the  alcohol,  then 
falling  sharply  when  the  subject  was  asleep,  rising  in  the  third  hour,  and 
remaining  at  a  high  level  (80  beats  and  over)  for  the  next  4  hours. 

Discussion  of  Composite  Chart  for  Mouth  Experiments. 

A  composite  chart  showing  the  results  of  the  ingestion  of  alcohol  by  mouth 
in  the  six  experiments  is  given  in  figure  67.  The  quantities  of  alcohol  taken 
varied  from  18.8  to  25  grams.  In  general,  therefore,  the  amounts  taken  were 
slightly  lower  than  those  in  the  rectal  experiments  with  a  7.5  per  cent  alcohol 
solution. 


138 


HUMAN  METABOLISM  WITH  ENEMATA. 


Pulse-rate. — The  average  pulse-rate  during  the  preliminary  portion  of 
the  experiments  was  between  66  and  67  beats  per  minute.  Immediately 
after  the  ingestion  of  alcohol  the  average  pulse-rate  was  nearly  70  beats. 
Presumably  this  was  almost  wholly  a  psychic  effect  due  to  the  taste  of  the 
alcohol  in  water,  for  the  pulse-rate  fell  thereafter  for  a  period  of  2  hours. 
It  then  began  to  rise,  reaching  74  beats  at  the  end  of  4  hours,  an  increase  of 
7  beats  over  the  preliminary  level.  Part  of  this  rise  was  undoubtedly  due 
to  the  fact  that  in  many  of  the  experiments  there  was  a  difference  in  sleep 
conditions,  as  the  subject  was  asleep  in  the  early  part  of  the  experiment  and 
awake  during  the  latter  part. 

Oxygen  absorption. — The  oxygen  absorption  in  the  preliminary  period 
was  about  245  c.  c.  Immediately  after  the  ingestion  of  alcohol  by  mouth, 
there  was  a  marked  rise,  part  of  which  was  due  to  the  activity  and  the  psychic 
effect  of  taking  the  alcohol.  During  the  first  half  hour  following  the  inges¬ 
tion  of  alcohol,  the  oxygen  absorption  fell  rapidly  until  it  reached  approxi¬ 
mately  235  c.  c.,  thus  falling  below  the  preliminary  value.  It  remained  at 


Fig.  67. — Chart  showing  compos¬ 
ite  results  for  measurements 
of  respiratory  quotient,  oxy¬ 
gen  absorption,  and  pulse- 
rate  in  6  experiments  with 
oral  ingestion  of  18.8  to  25 
grams  of  alcohol  in  solutions 
with  varying  concentra¬ 
tions.  (Mask.) 


COMPOSITE  CHART  ALCOHOL  SOLUTIONS  BY  MOUTH 


this  level  for  nearly  2\  hours,  then  rose  slightly  until  at  the  end  of  the  experi¬ 
mental  period,  4  hours  after  the  ingestion  of  alcohol,  it  was  slightly  higher 
than  the  average  value  during  the  preliminary  period.  It  is  questionable 
whether  this  change  was  due  to  the  alcohol  or  to  the  difference  in  sleep 
conditions,  as  in  some  of  the  experiments  the  subject  was  asleep  in  the  early 
part  of  the  experiment  and  awake  in  the  latter  part. 

Respiratory  quotient. — The  respiratory  quotient  shows  a  slightly  ascend¬ 
ing  value  during  the  preliminary  period,  with  an  average  of  about  0.82. 
Subsequent  to  the  taking  of  alcohol  there  was  at  first  a  high  quotient  of  0.85, 
from  which  it  fell  in  less  than  an  hour  to  0.77,  that  is,  0.05  below  the  pre¬ 
liminary  value.  During  the  second  hour  after  ingestion  the  quotient  rose 
slightly,  but  again  fell,  even  during  the  period  when  apparently  the  subject 
was  awake.  This  would  indicate  that  the  alcohol  produced  a  definite 
lowering  of  the  respiratory  quotient  which  was  present  during  the  entire 
4  hours  following  ingestion  by  mouth. 


RESPIRATORY  EXCHANGE  WITH  ALCOHOL  SOLUTIONS.  139 


General  Conclusions  Regarding  Experiments  with  Ingestion  of 

Alcohol  by  Mouth. 

We  have,  then,  a  slightly  different  picture  when  the  alcohol  is  given  by 
mouth  from  that  when  it  is  given  by  rectal  injection.  With  alcohol  taken 
by  mouth,  the  effect,  when  found,  is  quickly  apparent,  for  in  four  of  the 
six  experiments,  there  was  an  immediate  fall  in  the  respiratory  quotient  in 
the  first  half  hour,  while  with  rectal  feeding  the  fall  did  not  usually  take 
place  for  an  hour  and  a  half,  and  sometimes  more,  after  the  giving  of  the 
alcohol. 

These  experiments  were  conducted  primarily  as  a  comparison  series  to 
determine  whether  there  was  any  difference  in  the  metabolism  and  pulse- 
rate  when  alcohol  was  introduced  by  mouth  as  compared  with  that  intro¬ 
duced  by  rectum.  Unfortunately,  the  quantity  of  alcohol  used  in  these 
experiments  was  not  so  large  as  in  a  great  many  of  the  experiments  with  rec¬ 
tal  injection,  there  being  but  one  experiment  in  which  the  amount  intro¬ 
duced  was  25  grams. 

There  were  four  experiments  in  the  alcohol  series  in  which  400  c.  c.  of  a 
5  per  cent  alcohol  solution  were  injected,  and  it  is  thus  possible  to  compare 
the  results  of  the  mouth  experiments  with  those  in  which  a  like  amount  of 
alcohol  was  given  rectally.  On  inspecting  these  two  groups  we  find,  first, 
that  the  alcohol  given  by  mouth  lowered  the  respiratory  quotient  more 
promptly  than  it  did  with  rectal  injection,  although  the  lowering  of  the 
respiratory  quotient  was  of  about  the  same  order  and  if  anything  slightly 
greater  with  rectal  injection  than  with  ingestion  by  mouth.  As  seen  from 
the  studies  of  the  alcohol  in  the  urine,  the  peak  of  the  alcohol  concentration 
was  reached  about  the  same  time  with  introduction  by  mouth  or  by  rectum. 
Consequently,  the  lowering  of  the  respiratory  quotient  was  not  primarily 
due  to  the  earlier  appearance  of  an  increased  concentration  in  the  blood, 
and  there  must  be  a  difference  in  the  character  of  the  metabolism  or  the 
way  in  which  the  metabolism  changes  are  brought  about. 

The  decrease  or  lowering  of  the  respiratory  quotient  with  ingestion  of 
alcohol  by  mouth  occurred  so  promptly  that  it  is  hardly  conceivable  that 
it  was  due  wholly  to  the  maximum  concentration  of  alcohol  in  the  blood. 
It  more  likely  was  due  to  the  initiation  of  a  process  in  which  alcohol  takes  a 
part,  but  with  introduction  by  rectum  this  process  does  not  begin  so  promptly 
as  with  ingestion  by  mouth.  Whether  this  lag  with  rectal  introduction  is 
due  to  an  activity  of  the  liver  when  the  material  is  introduced  by  mouth 
and  its  inactivity  when  the  material  is  introduced  by  rectum  can  not  be 
shown  by  these  experiments,  but  it  may  be  offered  as  a  hypothesis  that  this 
is  the  cause.  On  the  other  hand,  with  rectal  introduction  of  alcohol,  the 
pulse-rate  increased  more  promptly  and  to  a  greater  extent  than  when  the 
alcohol  was  introduced  by  mouth;  in  fact,  with  400  c.  c.  of  a  5  per  cent  solu¬ 
tion  given  by  mouth,  there  was  very  little  increase  in  the  pulse-rate,  while, 
on  the  contrary,  when  the  material  was  introduced  rectally  the  increase  in 
the  pulse-rate  was  definite  in  3  out  of  4  experiments.  In  the  fourth  experi¬ 
ment  no  pulse-rate  was  taken.  We  thus  see  that  the  action  of  alcohol  upon 
the  metabolism  is  different,  according  to  whether  it  is  measured  by  the  re¬ 
spiratory  exchange  or  by  the  pulse-rate.  This  difference  will  be  discussed 
further  in  a  comparison  of  the  effects  of  rectal  feeding  and  mouth  feeding 
in  a  later  section.  (See  p.  189.) 


140 


HUMAN  METABOLISM  WITH  ENEMATA. 


RESPIRATORY  EXCHANGE  WITH  RECTAL  INJECTION  OF 

DEXTROSE. 

In  connection  with  this  research,  10  experiments  were  carried  out  in 
which  the  respiratory  exchange  was  determined  in  short  periods  before  and 
after  the  rectal  injection  of  solutions  of  dextrose;  7  of  the  experiments  were 
made  in  the  evening,  2  in  the  afternoon,  and  1  in  the  morning.  The  pro¬ 
cedure  was  the  same  as  for  the  experiments  with  the  solution  of  sodium 
chloride  and  with  the  alcohol  solutions.  The  sugar  used  (Kahlbaum’s 
purified  dextrose)  was  weighed  out  in  the  quantity  desired  and  dissolved 
in  a  0.6  per  cent  solution  of  sodium  chloride.  In  several  cases  10  drops  of 
tincture  of  opium  were  also  added.  In  2  experiments,  a  5  per  cent  solution 


Table  27. — Statistics  of  respiratory  exchange  observations  before  and  after  the  injection  by 
rectum  of  a  0.6  per  cent  solution  of  sodium  chloride  containing  dextrose. 


Subject. 

Date. 

Volume 

injected. 

Weight 

of 

dextrose. 

Duration 

of 

injection. 

Periods  before 
dextrose. 

Periods  after 
dextrose. 

No. 

Time 

covered. 

No. 

Time 

covered. 

1916. 

c.  c. 

grams. 

min. 

h. 

min. 

h.  min. 

A 

May  4 

500 

30 

94 

6 

1 

00 

24 

4  00 

May  9 

510 

“30 

88 

6 

1 

00 

22 

4  00 

C 

May  11 

510 

30 

29 

6 

1 

00 

17 

3  33 

D 

May  15 

510 

30 

42 

6 

1 

00 

21 

3  59 

C 

May  136 

510 

“30 

58 

c  18 

2 

58 

11 

2  6 

A 

Apr.  28 

1,000 

“60 

254 

0 

0 

00 

26 

5  3 

May  6 

d500 

30 

102 

6 

1 

00 

30 

5  00 

May  16 

d500 

“30 

87 

0 

0 

00 

24 

4  00 

1917. 

Feb.  22 6 

520 

“30 

99 

3 

1 

32 

12 

6  1 

C 

Apr.  17* 

•''500 

30 

81 

4 

2 

7 

8 

4  14 

“  Also  10  drops  of  tincture  of  opium. 

b  This  experiment  was  begun  1  hour  after  the  end  of  an  experiment  in  which  500  c.  c.  of  a  5  p.  ct. 
alcohol  solution  and  250  c.  c.  of  a  10  p.  ct.  alcohol  solution  were  injected  rectally. 

e  Includes  periods  before  and  after  injection  of  alcohol  solution  on  the  same  day.  (See  fig.  72.) 

d  The  dextrose  was  dissolved  in  a  5  per  cent  alcohol  solution  instead  of  in  a  0.6  per  cent  solution 
of  sodium  chloride. 

*  These  experiments  were  made  with  the  clinical  chamber  respiration  apparatus.  The  other 
dextrose  experiments  were  all  made  with  the  gasometer  and  mask  combination.  The  men 
were  in  the  lying  position  in  all  cases. 

f  The  dextrose  was  dissolved  in  500  c.  c.  of  distilled  water  instead  of  in  a  0.6  per  cent  solution 
of  sodium  chloride. 


of  alcohol  was  substituted  for  the  solution  of  sodium  chloride;  8  of  the  10 
experiments  were  carried  out  by  means  of  the  mask,  valves,  gasometer,  and 
gas  analysis.  The  remaining  2  experiments  (February  22  and  April  17, 
1917)  were  made  with  the  clinical  respiration  apparatus  1  in  the  morning, 
with  the  subject  in  the  post-absorptive  condition,  the  last  meal  having 
been  taken  the  evening  before. 

A  list  of  the  observations,  with  subject,  date,  amount  of  dextrose  injected, 
and  the  number  of  periods,  is  given  in  table  27.  Three  subjects,  A,  C,  and 
D,  were  employed.  The  weight  of  dextrose  used  was  30  grams  in  a  volume 
of  500  to  520  c.  c.,  except  on  April  28,  when  it  was  60  grams  in  a  volume  of 
1,000  c.  c.  The  time  of  injection  varied  from  29  minutes  on  May  11,  1916, 


1  Benedict  and  Tompkins:  Boston  Med.  and  Surg.  Journ.,  1916,  174,  pp.  857,  898,  and  939. 


RESPIRATORY  EXCHANGE  WITH  DEXTROSE. 


141 


to  254  minutes  on  April  28, 1916.  With  one  exception,  the  number  of  periods 
before  injection  ranged  between  none  on  April  28  and  May  16  and  6  on  5 
days.  On  May  13  the  number  of  periods  before  injection  of  the  dextrose 


SUBJECT  A.  MAY  4.  1916 

30  Gms.  DEXTROSE  IN  500  c.c.NaCl  SOLUTION  MASK 


Fig.  68. — Respiratory  quotient,  oxygen  absorption,  and  pulse- 
rate  of  subject  A,  May  4,  1916,  before  and  after  rectal 
injection  of  30  grams  of  dextrose  in  500  c.  c.  of  a  0.6  per 
cent  solution  of  sodium  chloride.  (Mask,  with  continu¬ 
ous  observation.) 

The  horizontal  line  at  the  bottom  of  this  and  subse¬ 
quent  charts  gives  a  record  of  sleep,  the  solid  portions 
indicating  when  the  subject  was  asleep  and  the  broken 
portions  when  the  subject  was  awake. 


SUBJECT  A.  MAY  9.  1916 

30  Gms.  DEXTROSE  IN  510  c.c.NaCl  SOLUTION  MASK 


Fig.  69. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate 
of  subject  A,  May  9,  1916,  before  and  after  rectal  injection  of 
30  grams  of  dextrose  in  510  c.  c.  of  a  0.6  per  cent  solution 
of  sodium  chloride.  (Mask,  with  continuous  observation.) 

was  18,  but  this  number  includes  the  periods  before  and  after  injection 
of  solutions  of  alcohol  on  the  same  day.  The  time  covered  by  the  prelimi¬ 
nary  periods  varied  from  1  hour  to  2  hours  and  58  minutes.  The  length  of 


142 


HUMAN  METABOLISM  WITH  ENEMATA. 


the  individual  periods  was  usually  about  10  minutes,  except  in  the  2  experi¬ 
ments  with  the  clinical  chamber,  in  which  it  was  approximately  30  minutes. 
The  number  of  periods  after  the  injection  began  varied  from  11  to  30  in 
the  experiments  with  the  gasometer  method  and  10-minute  periods,  and 
from  8  to  12  in  the  experiments  with  the  clinical  respiration  chamber. 


SUBJECT  C.  MAY  11.  1916 

30  Gms.  DEXTROSE  IN  510c.o.  NaCI  SOLUTION  MASK 


Fig.  70. — Respiratory  quotient,  oxygen  absorption, 
and  pulse-rate  of  subject  C,  May  11,  1916,  before 
and  after  rectal  injection  of  30  grams  of  dextrose 
in  510  c.  c.  of  a  0.6  per  cent  solution  of  sodium 
chloride.  (Mask,  with  continuous  observation.) 


SUBJECT  D.  MAY  15.  1916 

30  Gms.  DEXTROSE  IN  510  c  c.  NaCI  SOLUTION  MASK 


Fig.  71. — Respiratory  quotient,  oxygen  absorption,  and  pulse- 
rate  of  subject  D,  May  15,  1916,  before  and  after  rectal 
injection  of  30  grams  of  dextrose  in  510  c.  c.  of  a  solution 
of  sodium  chloride.  (Mask,  with  continuous  observation.) 

The  discussion  of  the  results  of  these  observations  follows,  the  method  of 
treatment  being  the  same  as  that  for  the  preceding  series,  with  charts 
(figs.  68  to  77)  showing  the  respiratory  quotient,  oxygen  absorption,  and 
pulse-rate  for  each  experiment.  The  determinations  of  the  absorption  of  the 
dextrose  have  already  been  considered.  (See  pp.  30  to  33.) 


RESPIRATORY  EXCHANGE  WITH  DEXTROSE. 


143 


Results  of  Measurements  Before  Rectal  Injection. 

With  subject  A,  on  May  6,  the  last  food  was  at  8  a.  m.,  while  the  first 
period  of  the  experiment  was  at  lh  39m  p.  m.  On  May  4  and  May  9  the 

SUBJECT  C  MAY  ia  1916 

500  c.c.  5  PER  CENT  ALCOHOL  250  c.a  10  PER  CENT  ALCOHOL 


30  Gms.  DEXTROSE  510  o.  c.  NaCl  SOLUTION  MASK 


OF  ALCOHOL  BEGAN  HALF  HOURS  AFTER  RECTAL 

INJECTION  OF  DEXTROSE  BEGAN 

Fig.  72. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  C, 
May  13,  1916,  before  and  after  rectal  injection  of  500  c.  c.  of  a  5  per  cent 
alcohol  solution  and  250  c.  c.  of  a  10  per  cent  alcohol  solution,  and  after  a 
second  injection  of  30  grains  of  dextrose  in  510  c.  c.  of  a  0.6  per  cent  solution 
of  sodium  chloride.  (Mask,  with  continuous  observation.) 


SUBJECT  A  APR.  28.  1916 

60  Gms.  DEXTROSE  IN  1000  c.c.  NaCl  SOLUTION  MASK 


Fig.  73. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate 
of  subject  A,  April  28,  1916,  after  rectal  injection  of  60  grams 
of  dextrose  in  1,000  c.  c.  of  a  0.6  per  cent  solution  of  sodium 
chloride.  (Mask,  with  continuous  observation.) 

last  food  was  at  lh  30m  p.  m.,  while  the  first  periods  were  at  6h  29m 
and  5h  Q5m  p.  m.,  respectively.  The  two  experiments  with  A  on  May 
16  and  April  28  were  carried  out  in  the  early  part  of  the  evening,  with 
food  presumably  at  noon,  although  no  record  was  made  at  the  time. 


144 


HUMAN  METABOLISM  WITH  ENEMATA. 


With  C  on  May  11,  the  last  food  was  at  lh  30m  p.  m.  and  the  first 
period  began  at  5h  56m  p  m.  On  May  13  the  subject  had  at  8  a.  m.  a 
cupful  of  coffee  with  2  teaspoonfuls  of  sugar;  the  first  period  began  at 


SUBJECT  A.  MAY  6.  1916 

30  Gms.  DEXTROSE  IN  500  c.c.  5  PER  CENT  ALCOHOL  MASK 


Fig.  74. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  sub¬ 
ject  A,  May  6,  1916,  before  and  after  rectal  injection  of  30  grams  of 
dextrose  in  500  c.  c.  of  a  5  per  cent  alcohol  solution.  (Mask,  with 
continuous  observation.) 


SUBJECT  A  MAY  16.  1916  MASK 

30  Gms  DEXTROSE  IN  500  c  c  5  PER  CENT  ALCOHOL 


Fig.  75. — Respiratory  quotient,  oxygen  absorption, 
and  pulse-rate  of  subject  A,  May  16,  1916,  after 
rectal  injection  of  30  grams  of  dextrose  in  500  c.  c. 
of  a  5  per  cent  alcohol  solution.  (Mask,  with 
continuous  observation.) 

9h  50m  a.  m.  With  subject  D,  on  May  15,  the  last  food  was  at  8  a.  m. 
and  the  first  period  began  at  2h  20m  p.  m. 

Pulse-Rate. 

The  preliminary  pulse-rates  for  subject  A  in  the  two  experiments  on  May  4 
and  9  were  59  and  61  beats  per  minute,  respectively.  On  May  6,  1916,  and 


RESPIRATORY  EXCHANGE  WITH  DEXTROSE. 


145 


February  22,  1917,  they  averaged  63  beats  for  both  experiments.  In  the 
latter  experiment  the  subject  was  in  the  post-absorptive  condition.  There 
were  no  preliminary  periods  on  May  16  and  on  April  28.  With  subject  C, 
the  preliminary  pulse-rate  on  May  11  was  57  beats  and  on  May  13  and  April 


SUBJECT  A.  FEB.  22.  1917 

30  Grrts.  DEXTROSE  IN  520  c.c.  NaCI  SOLUTION  CHAMBER  RESPIRATION  APPARATUS 


Fig.  76. — Respiratory  quotient,  oxygen  absorption,  carbon-dioxide  elimination,  and  pulse-rate  of 
subject  A,  February  22,  1917,  before  and  after  rectal  injection  of  30  grams  of  dextrose  in  520 
c.  c.  of  a  0.6  per  cent  solution  of  sodium  chloride.  (Chamber  respiration  apparatus.) 


SUBJECT  C.  APR.  17.  1917 

30  Gms.  DEXTROSE  IN  500  c.c  DISTILLED  WATER  CHAMBER  RESPIRATION  APPARATUS 


Fig.  77. — Respiratory  quotient,  oxygen  absorption,  carbon-dioxide  elimination,  and  pulse- 
rate  of  subject  C,  April  17,  1917,  before  and  after  rectal  injection  of  30  grams  of  dextrose 
in  500  c.  c.  of  distilled  water.  (Chamber  respiration  apparatus.) 


146 


HUMAN  METABOLISM  WITH  ENEMATA. 


17  it  was  63  beats.  On  April  17,  C  was  in  a  post-absorptive  condition. 
With  subject  D,  the  average  pulse-rate  for  the  six  periods  before  the 
injection  took  place  was  74  beats.  The  pulse-rates,  therefore,  for  both 
subjects  A  and  C  were  near  their  basal  pulse-rates,  which  for  subject  A  was 
64  beats  and  for  subject  C  65  beats.  (See  table  1,  p.  22.)  No  basal 
pulse-rate  is  available  for  subject  D. 

Oxygen  Absorption. 

The  average  oxygen  absorption  before  injection  of  subject  A  on  May  4  was 
196  c.  c.  per  minute,  on  May  6,  198  c.  c.,  and  on  May  9,  211  c.  c.  On  Feb¬ 
ruary  22,  1917,  when  he  was  in  a  post-absorptive  condition,  it  was  204  c.  c. 
per  minute.  All  these  values  closely  approximate  his  basal  absorption  of 
206  c.  c.,  given  in  table  1,  page  22.  With  subject  C,  on  May  11,  the  prelim¬ 
inary  average  was  271  c.  c.  per  minute,  on  May  13,  261  c.  c.,  and  on  April  17, 
1917,  251  c.  c.  These  values  were  somewhat  lower  than  the  average  basal 
value  for  this  subject  of  285  c.  c.  (See  table  1.)  With  subject  D,  the  average 
absorption  before  injection  was  215  c.  c.  per  minute,  which  is  a  somewhat 
low  average  for  this  individual. 

Respiratory  Quotient. 

The  preliminary  respiratory  quotients  in  four  of  these  experiments  were 
somewhat  higher  than  in  the  majority  of  experiments  heretofore  considered. 
With  subject  A,  on  May  4,  the  quotient  was  0.82,  on  May  6,  0.85,  and  on  May 
9,  0.86.  On  February  22  (the  post-absorptive  day)  it  was  0.87.  With 
subject  C,  the  respiratory  quotients  on  May  11  and  April  17  were  0.80  and 
0.84,  respectively.  On  May  13  it  was  high,  being  0.89.  This  was  the  ex¬ 
periment  in  which  C  had  a  cupful  of  coffee  and  2  teaspoonfuls  of  sugar  at 
8  a.  m.  and  the  experiment  began  at  about  10  a.  m.  The  respiratory  quotient 
before  injection  with  subject  D  on  May  15  was  0.79.  These  quotients  were, 
therefore,  not  entirely  ideal  for  the  study  of  a  superimposed  condition,  which 
would  tend  to  raise  the  respiratory  quotient,  namely,  the  ingestion  of  dex¬ 
trose. 

Results  of  Measurements  After  Rectal  Injection  of  Dextrose 

(Gasometer  Method). 

In  the  first  four  experiments  considered  in  this  section,  30  grams  of  dex¬ 
trose  were  given  in  approximately  500  c.  c.  of  a  solution  of  sodium  chloride. 
Two  of  these  experiments  were  with  subject  A,  one  with  subject  C,  and  one 
with  subject  D.  In  the  two  experiments  with  subject  A,  there  was  an  indi¬ 
cation  of  a  marked  rise  in  the  respiratory  quotient.  In  the  experiment  on 
May  4,  the  rise  began  about  2  hours  after  the  beginning  of  the  injection,  and 
in  the  experiment  on  May  9  this  rise  was  a  little  earlier,  i.  e.,  lj  to  2  hours 
after  the  dextrose,  with  a  tendency  to  a  decline  afterward.  In  the  experi¬ 
ment  with  subject  C  (May  11),  there  was  some  indication  of  a  rise  in  the 
quotient  about  1  hour  after  the  solution  was  given.  With  subject  D  there 
was  very  little  indication  of  any  real  change  in  the  quotient.  In  three 
experiments  out  of  four,  therefore,  with  30  grams  of  dextrose  and  500  c.  c.  of 
a  sodium-chloride  solution,  the  respiratory  quotient  rose  in  1  to  2  hours  after 
the  flow  of  the  solution  began.  The  time  of  change  is  comparable  with  that 
indicated  in  the  experiments  with  rectal  introduction  of  alcohol. 


RESPIRATORY  EXCHANGE  WITH  DEXTROSE. 


147 


The  oxygen  absorption  in  the  two  experiments  with  subject  A  shows  a 
slight  tendency  to  increase  within  2  hours  after  the  introduction  of  the  solu¬ 
tion  commenced.  The  increase  on  May  9  was  somewhat  more  positive  than 
that  on  May  4,  but  this  increase  is  coincident  with  the  awakening  of  the 
subject  from  sleep.  In  the  experiment  with  subject  C  there  was  also  a  slight 
change  in  the  oxygen  absorption  in  the  last  hour  of  the  experiment,  but  this 
again  is  coincident  with  the  wakening  of  the  subject.  In  the  experiment 
with  subject  D  there  was  no  evidence  of  a  change  in  the  oxygen  absorption 
until  about  3J  hours  after  the  beginning  of  the  injection,  and  this  rise  oc¬ 
curred  immediately  after  the  subject  was  obliged  to  urinate. 

The  pulse-rates  in  the  four  experiments  tended  to  rise,  also,  but  in  at  least 
two  of  the  experiments  this  change  occurred  when  the  subject  awakened. 
The  rise  in  the  pulse-rate  in  the  experiment  with  subject  A  on  May  4  was, 
however,  independent  of  such  change  in  conditions  of  sleep.  * 

Summarizing  the  results  of  these  four  experiments,  we  find  a  positive  rise 
in  the  respiratory  quotient,  a  positive  increase  in  the  pulse-rate  occurring 
within  3  hours,  and  some  increase  in  the  oxygen  absorption.  This  amount  of 
dextrose  is  very  small  in  comparison  with  the  quantities  usually  given  by 
mouth  in  studies  of  carbohydrates  in  which  50,  75,  and  even  100  grams  have 
ordinarily  been  ingested.  It  is  surprising,  therefore,  that  so  small  an  amount 
of  dextrose  as  was  given  in  the  experiments  here  discussed  should  produce 
any  material  change  in  either  the  respiratory  quotient  or  the  oxygen  absorp¬ 
tion,  and  especially  in  the  pulse-rate.  The  proportion  of  the  total  metabo¬ 
lism  which  was  supplied  by  the  dextrose  thus  utilized  and  the  percentage 
effect  upon  the  total  metabolism  are  considered  later  in  the  general  discus¬ 
sion  of  results.  (See  p.  186.) 

One  experiment  was  made  with  subject  A,  on  April  28,  1916,  in  which  60 
grams  of  dextrose  were  given  in  1,000  c.  c.  of  a  solution  of  sodium  chloride  in 
the  course  of  4J  hours.  The  introduction  of  this  amount  resulted  in  a  very 
positive  and  gradual  increase  in  the  respiratory  quotient  in  the  dextrose 
periods,  which  began  1J  hours  after  the  flow  of  the  solution  started,  and  al¬ 
though  somewhat  irregular  in  its  course,  continued  throughout  the  rest  of  the 
experiment  (3J  hours).  The  pulse-rate,  on  the  other  hand,  did  not  change 
materially.  While  the  oxygen  absorption  was  somewhat  irregular  from 
period  to  period,  apparently  it  was  likewise  uninfluenced  by  the  carbohy¬ 
drate. 

There  were  two  experiments,  both  with  subject  A,  in  which  30  grams  of 
dextrose  were  given  in  500  c.  c.  of  a  5  per  cent  alcohol  solution.  The  object 
of  these  two  experiments  was  to  determine  which  material  would  predomi¬ 
nate  in  the  metabolism  as  shown  by  the  respiratory  quotient  when  alcohol 
and  dextrose  were  given  simultaneously.  In  the  experiment  on  May  6 
there  was  a  noticeable  decrease  in  the  respiratory  quotient  which  began 
shortly  after  the  injection  commenced  and  reached  its  lowest  level  near  the 
end  of  the  second  hour.  The  average  respiratory  quotient  before  the  in¬ 
jection  commenced  was  0.86;  after  the  injection  it  fell  on  the  average  as 
low  as  0.77.  It  might  appear  that  part  of  this  fall  was  due  to  the  height  of 
the  initial  respiratory  quotient.  This  may  have  been  true,  but  the  entire 
fall  can  not  be  ascribed  to  a  natural  lowering  of  the  respiratory  quotient 
from  the  initial  high  value.  In  all  probability,  the  alcohol  was  effective  in 
lowering  the  respiratory  quotient,  in  spite  of  the  fact  that  dextrose  was 


148 


HUMAN  METABOLISM  WITH  ENEMATA. 


simultaneously  given.  In  other  words,  the  alcohol  was  utilized  rather  than 
the  dextrose,  or  enough  alcohol  was  made  use  of  to  offset  the  increase  due 
to  utilization  of  dextrose. 

In  the  experiment  on  May  16  there  were  no  preliminary  periods;  hence  we 
have  no  data  as  to  the  initial  respiratory  quotient.  The  general  level  of  the 
quotient  was  not  altered  during  the  experiment,  so  that  in  this  case  there  was 
neither  an  increase  due  to  the  utilization  of  dextrose  nor  a  fall  due  to  the 
utilization  of  alcohol,  or  if  such  use  took  place,  the  two  substances  counter¬ 
balanced  one  another  in  their  effect. 

The  oxygen  absorption  in  the  experiment  on  May  6  began  to  increase 
within  the  first  hour  and  rose  to  a  level  25  c.  c.  higher  than  that  for  the  pre¬ 
liminary  period,  and  continued  on  this  level  for  2\  hours.  At  the  end  of  the 
fourth  hour  the  oxygen  values  rose  still  higher.  At  this  time,  however,  the 
subject  woke  up  and  remained  awake  for  the  rest  of  the  experiment.  In  the 
experiment  on  May  16,  the  general  level  of  the  oxygen  absorption  remained 
practically  unaltered  for  about  3  hours  after  the  beginning  of  the  injection. 
In  the  fourth  hour  after  injection,  it  was  increased  materially  from  10  to 
15  c.  c.  per  minute. 

The  pulse-rate  with  the  subject  on  May  6  increased  from  a  preliminary 
average  value  of  63  beats  to  a  value  of  74  beats  in  the  course  of  3  hours. 
When  the  subject  awoke  at  the  end  of  the  fourth  hour,  it  changed  from  the 
level  of  74  beats  to  one  of  over  85  beats.  In  the  experiment  on  May  16,  the 
pulse-rate  was  very  irregular  for  the  first  1J  hours  after  injection  and  the  gen¬ 
eral  level  was  below  70  beats.  During  the  next  hour  it  averaged  73  beats  and 
the  general  level  for  the  last  2\  hours  of  the  experiment  was  higher  than  the 
1§  hours  preceding.  There  was  thus  an  increase  in  the  pulse-rate  which  is  in 
line  with  the  other  experiments  and  presumably  due  chiefly  to  the  influence 
of  alcohol.  In  the  experiment  on  May  6,  it  would  appear  as  though  both 
alcohol  and  dextrose  influenced  the  results. 

There  was  an  experiment  on  May  13  with  subject  C,  which  was  in  reality 
composed  of  two  parts.  In  the  first  section  of  the  experiment,  after  the  pre¬ 
liminary  period,  500  c.  c.  of  a  5  per  cent  alcohol  solution,  and  250  c.  c.  of  a 
10  per  cent  alcohol  solution,  or  50  grams  of  alcohol  in  all,  were  given  to  the 
subject  over  a  period  of  2  hours.  There  was  then  a  rest  of  about  an  hour. 
At  the  end  of  the  rest  period  he  was  given  30  grams  of  dextrose  in  500  c.  c.  of 
0.6  per  cent  sodium-chloride  solution.  The  object  of  this  experiment  was  to 
determine  when  the  effect  of  the  rectal  injection  of  alcohol  was  ended  and 
whether  dextrose,  injected  later  than  the  alcohol,  would  alter  the  metabolism. 

The  pulse-rate  indicated  the  greatest  change,  being  markedly  depressed  by 
a  period  of  sleep  which  occurred  in  the  second  half  hour,  and  falling  from  63 
to  56  beats.  When  the  subject  awoke,  the  pulse-rate  rose  considerably 
above  the  pulse-rate  in  the  preliminary  periods,  or  68  beats  as  compared  with 
63  beats.  After  the  period  of  rest  following  the  alcohol  section  of  the  ex¬ 
periment,  the  pulse-rate  again  fell  to  a  generally  low  level  and  remained 
there  with  some  variation  throughout  the  rest  of  the  experiment. 

The  oxygen  absorption  was  slightly  increased  in  the  second  hour  after  the 
beginning  of  the  alcohol  injection,  but  in  the  period  during  which  the  dex¬ 
trose  solution  was  given,  the  oxygen  absorption  was  materially  lowered. 
Therefore  the  dextrose  injection  did  not  produce  a  stimulating  effect  upon 
the  total  metabolism. 


RESPIRATORY  EXCHANGE  WITH  DEXTROSE. 


149 


The  average  respiratory  quotient  of  0.88  in  the  preliminary  period  was 
somewhat  high  upon  which  to  superimpose  the  effect  of  alcohol.  As  would 
naturally  be  expected,  the  quotient  fell  from  this  level,  dropping  to  0.75 
during  a  period  of  sleep  in  the  second  half  hour  after  injection.  This  fall 
was  presumably  due  to  both  alcohol  and  sleep.  When  the  subject  was  awake 
in  the  last  half  hour  of  the  alcohol  experiment  the  quotient  was  slightly 
lower  than  in  the  preliminary  period.  During  the  period  of  time  beginning 
3  hours  after  the  injection  of  alcohol  commenced,  when  dextrose  was  in¬ 
jected,  the  respiratory  quotient  was  on  a  generally  lower  level  than  at  any 
time  preceding  it,  with  apparently  no  influence  of  dextrose  upon  the  respira¬ 
tory  quotient.  In  general,  it  would  appear  as  if  the  main  influence  was  due 
to  alcohol,  although  the  fall  was  not  so  large  as  would  be  expected  with  this 
large  amount  of  alcohol  (50  grams) . 


Results  of  Measurements  After  Rectal  Injection  of  Dextrose 

(Chamber  Method). 

The  two  experiments  with  the  clinical  respiration  chamber  (February  22 
and  April  17)  indicate  some  increase  in  pulse-rate  which  is  caused  in  part  by 
the  awakening  of  the  subject,  but  also  due  in  part  to  the  rectal  injection  of 
dextrose.  In  both  the  experiments  the  respiratory  quotient  shows  slight 
increases  (0.02  to  0.05),  occurring  2  to  3  hours  after  the  injection.  The  oxy¬ 
gen  absorption  in  one  experiment,  that  with  A  on  February  22,  rose  after  3 
hours  and  in  the  other  immediately  after  injection. 


COMPOSITE  CHART  RECTAL  INJECTION  OF  DEXTROSE  IN  0  6  PER  CENT 
SODIUM  CHLORIDE  SOLUTION 


Fig.  78. — Chart  showing  composite  results  for  measurements 
of  respiratory  quotient,  oxygen  absorption,  and  pulse-rate 
in  9  experiments  with  rectal  injection  of  30  grams  of  dex¬ 
trose  in  solution.  (Mask  or  clinical  respiration  chamber.) 


Discussion  of  Composite  Chart. 

The  composite  chart  for  the  dextrose  series  is  given  in  figure  78.  This 
chart  includes  all  of  the  experiments  with  30  grams  of  dextrose  made  by  the 
two  methods. 

Pulse-rate. — The  pulse-rate  during  the  preliminary  period  was  nearly  the 
same  as  the  composite  for  the  experiments  when  alcohol  was  taken  by  mouth. 
(See  fig.  67,  p.  138.)  In  the  pre-injection  period  it  varied  from  66  to  63  beats 
per  minute.  During  the  first  hour  after  injection  there  was  little  alteration, 
but  at  the  end  of  the  first  hour  the  pulse-rate  began  to  rise  and  rose  grad¬ 
ually  until  during  the  fourth  hour  it  was  nearly  70  beats  per  minute. 
There  was  thus  a  definite  rise  in  the  average  pulse-rate  during  the  observa¬ 
tions,  due  to  the  injection  of  the  dextrose  solution. 


150 


HUMAN  METABOLISM  WITH  ENEMATA. 


Oxygen  absorption. — The  oxygen  absorption  in  the  preliminary  40  minutes 
fell  from  235  c.  c.  to  225  c.  c.,  and  continued  to  decrease  for  1J  hours  after 
the  dextrose  injection  began.  It  remained  unaltered  for  about  an  hour, 
then  rose  again,  but  the  average  absorption  did  not  at  any  time  rise  to  the 
average  value  for  the  preliminary  period.  It  would  appear  that  dextrose 
exercised  slight,  if  any,  effect  upon  the  average  oxygen  absorption,  al¬ 
though  some  of  the  individual  experiments  did  show  some  increase. 

Respiratory  quotient. — During  the  preliminary  period  the  respiratory 
quotient  fell  markedly.  After  the  injection  it  rose  again,  although  during 
the  first  hour  it  did  not  reach  the  preliminary  level.  This  increase  continued 
until  in  the  third  hour  after  injection  it  was  considerably  above  the  prelimi¬ 
nary  value,  being  0.86  as  compared  with  0.81.  This  level  was  maintained 
until  nearly  the  end  of  the  experiment,  that  is,  4  hours  after  injection. 
Whether  this  increase  was  caused  by  the  dextrose  injection  or  whether  such 
injection  favored  an  increased  utilization  of  carbohydrate  is  not  known. 
The  rise  of  the  respiratory  quotient  definitely  indicates  an  increase  in  the 
metabolism  of  carbohydrates. 

General  Conclusions  Regarding  Respiratory  Exchange  with 
Rectal  Introduction  of  Dextrose. 

The  rectal  injection  of  30  grams  of  dextrose  in  500  c.  c.  of  a  sodium- 
chloride  solution  caused  a  rise  in  pulse-rate  of  5  beats  per  minute  in  2  to  3 
hours  after  injection.  It  also  increased  the  respiratory  quotient  0.02  to  0.05 
in  2  to  3  hours  after  the  injection  began. 

In  the  majority  of  the  experiments  the  oxygen  consumption  increased 
slightly,  this  increase  taking  place  either  immediately  or  within  2  hours  after 
the  injection  began.  When  the  dextrose  was  given  in  a  5  per  cent  alcohol 
solution  there  was  no  increase  in  the  respiratory  quotient,  but  there  was  an 
increase  in  both  pulse-rate  and  oxygen  consumption.  This  effect  is  con¬ 
sidered  to  be  due  more  especially  to  the  effect  of  alcohol  than  to  the  injection 
of  the  dextrose  solution.  Even  on  the  day  when  alcohol  was  given  in  the 
morning  and  dextrose  solution  in  the  afternoon,  there  was  no  apparent  effect 
upon  the  metabolism  due  to  the  introduction  of  the  dextrose. 

The  increase  in  the  respiratory  quotient  after  the  giving  of  dextrose  by 
rectum  must  indicate  an  increase  in  utilization  of  the  dextrose  injected  or 
else  bring  about  a  condition  in  which  there  is  an  increase  in  the  proportion  of 
carbohydrate  in  the  metabolism.  The  amount  of  carbohydrate  which  is 
metabolized  under  these  conditions  is  considered  in  a  later  section  in  the 
theoretical  discussion  of  results.  (See  p.  186.) 

RESPIRATORY  EXCHANGE  WITH  RECTAL  INJECTION  OF 

LEVULOSE. 

A  series  of  experiments  to  determine  the  effect  of  the  rectal  injection  of 
levulose  upon  the  respiratory  exchange,  with  particular  reference  to  its  effect 
upon  the  respiratory  quotient  and  the  oxygen  absorption,  was  carried  out  in 
the  early  part  of  1916,  and,  in  fact,  before  the  series  with  dextrose  just  dis¬ 
cussed. 

The  subjects  were  the  same  as  those  used  in  the  study  with  dextrose, 
viz,  A,  C,  and  D.  Kahlbaum’s  commercial  grade  of  levulose  was 


RESPIRATORY  EXCHANGE  WITH  LEYULOSE. 


151 


employed.1  The  method  of  preparing  the  solution  and  the  experimental 
procedure  were  likewise  the  same  as  in  the  dextrose  experiments. 

The  number  and  character  of  the  experiments  are  shown  in  table  28;  the 
graphic  records  are  given  in  figures  79  to  88.  The  levulose  was  in  all  cases 
administered  in  a  0.6  per  cent  solution  of  sodium  chloride.  In  4  experiments 
25  grams  of  levulose  were  given  in  a  volume  of  500  c.  c.,  in  1  experiment  37.5 
grams  in  a  volume  of  750  c.  c.,  in  2  experiments  50  grams  in  a  volume  of  1,000 
c.  c.,  and  in  3  experiments  the  same  amount  in  a  volume  of  500  c.  c.  The 
duration  of  the  injection  varied  from  19  minutes  to  129  minutes.  The  num¬ 
ber  of  periods  in  which  the  respiratory  exchange  was  measured  before  injec¬ 
tion  varied  from  4  to  9  and  the  time  covered  by  these  periods  from  40  minutes 
to  1  hour  and  30  minutes.  The  number  of  periods  after  the  injection  began 
varied  from  13  to  26  and  the  time  covered  from  2  hours  and  9  minutes  to  4 
hours  and  20  minutes. 


Table  28. — Statistics  of  respiratory  exchange  observations  before  and  after  the  injection  by 
rectum  of  0.6  per  cent  solution  of  sodium  chloride  containing  levulose. 


Subject. 

Date.0 

Volume 

Weight 

of 

levulose. 

Duration 

of 

injection. 

Periods  before 
levulose. 

Periods  after 
levulose. 

injected. 

No. 

Time 

covered. 

No. 

Time 

covered. 

C. 

1916. 
Feb.  1 

c.  c. 

500 

grams. 

25.0 

min. 

95 

7 

h.  min. 

1  10 

19 

h.  min. 

3  10 

Feb. 

7 

500 

6  25.0 

19 

6 

1 

00 

17 

2  50 

D. 

Feb. 

3 

500 

25.0 

62 

6 

1 

00 

17 

2  50 

Feb. 

11 

500 

6  25.0 

30 

9 

1 

24 

16 

2  39 

C. 

Feb. 

15 

750 

6  37.5 

57 

4 

0 

40 

16 

2  40 

Jan. 

25 

1,000 

6  50.0 

99 

6 

1 

00 

20 

3  21 

D. 

Jan. 

28 

1,000 

50.0 

129 

9 

1 

30 

13 

2  9 

A. 

Jan. 

15 

500 

50.0 

29 

7 

1 

10 

15 

2  38 

Jan. 

18 

500 

50.0 

95 

7 

1 

11 

26 

4  20 

C. 

Jan. 

12 

500 

50.0 

54 

6 

1 

00 

19 

3  34 

°  All  of  the  levulose  experiments  were  made  with  the  gasometer  and  mask  combination. 
b  Also  5  to  6  drops  of  tincture  of  opium. 


Results  of  Measurements  Before  Rectal  Injection. 

The  conditions  under  which  these  experiments  were  carried  out  were 
practically  the  same  as  in  the  previous  groups.  All  but  two  observations  be¬ 
gan  between  5  and  6  p.  m.  The  experiment  with  A,  January  15,  began  at 
2h  30m  p.  m.,  and  on  January  18  at  3h  20m  p.  m.  No  food  was  taken 
after  8h  15ra  a.  m.  on  any  day.  On  January  15  and  January  18,  the  first 
period  began  within  10  minutes  after  the  subject  lay  down,  and  on  January 
12  in  20  minutes.  In  all  the  other  experiments  there  was  at  least  a  half 
hour  of  preliminary  rest  before  the  first  period  recorded  in  the  curves. 

Pulse-Rate. 

The  average  preliminary  pulse-rate  for  subject  A  was  60  beats  on  January 
15  and  70  beats  on  January  18,  as  compared  with  the  basal  pulse-rate  of 

*  The  levulose  was  the  same  as  that  used  in  a  previous  study  by  Joslin  (Joslin:  Carnegie  Inst. 
Wash.  Pub.  No.  323,  1923,  p.  213),  and  contained,  according  to  previous  analysis,  4.8  per  cent 
of  moisture.  In  reporting  the  results  of  both  researches,  however,  the  moisture  in  the  levulose 
has  not  been  taken  into  consideration. 


152 


HUMAN  METABOLISM  WITH  ENEMATA. 


64  beats  reported  for  this  subject  in  table  1,  page  22.  The  averages  for  C 
ranged  before  injection  from  62  beats  on  February  7  to  66  beats  on  January  12. 
His  basal  pulse  as  given  in  table  1,  page  22,  was  65  beats.  The  average 
rates  in  the  preliminary  periods  with  D  ranged  from  71  to  80  beats. 


SUBJECT  C.  FEB.  I  1916.  MASK 

25  G rns._  LEVULOSE.IN _  5QQ  C^C.  NaCl  SQCDTION 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 

79 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 
80 


Fig.  79. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  C,  February  1, 
1916,  before  and  after  rectal  injection  of  25  grams  of  levulose  in  500  c.  c.  of  a  0.6  per  cent 
solution  of  sodium  chloride.  (Mask,  with  continuous  observation.) 

Fig.  80. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  C,  February  7, 
1916,  before  and  after  rectal  injection  of  25  grams  of  levulose  in  500  c.  c.  of  a  0.6  per  cent 
solution  of  sodium  chloride.  (Mask,  with  continuous  observation.) 


SUBJECT  D.  FEB.  11.  1916.  MASK 

25  Gms.  LEVULOSE  IN  500  c.c.NaCI  SOLUTION 


SUBJECT  D.  FEB.  3.  1916.  MASK 

25  Gms.  LEVULOSE  IN  500  j?.  c„NaCI  SOLUTION 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN  HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


81  82 

Fig.  81. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  D,  February  3,  1916* 
before  and  after  rectal  injection  of  25  grams  of  levulose  in  500  c.  c.  of  a  0.6  per  cent  solution  of 
sodium  chloride.  (Mask,  with  continuous  observation.) 

Fig.  82. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  D,  February  11, 
1916,  before  and  after  rectal  injection  of  25  grams  of  levulose  in  500  c.  c.  of  a  0.6  per  cent 
solution  of  sodium  chloride.  (Mask,  with  continuous  observation.) 

The  horizontal  line  at  the  bottom  of  this  and  subsequent  charts  gives  a  record  of  sleep, 
the  solid  portions  indicating  when  the  subject  was  asleep,  and  the  broken  portions  when  he 
was  awake. 


RESPIRATORY  EXCHANGE  WITH  LEYULOSE. 


153 


Oxygen  Absorption. 

The  average  oxygen  absorption  before  injection  for  A  was  201  c.  c.  on 
January  15  and  223  c.  c.  on  January  18.  As  his  basal  oxygen  consumption 


SUBJECT  C  FEB.  15,  1916.  MASK 

37.5  Gms.  LEVULOSE  IN  750  o.c.  NaCl  SOLUTION 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


83 


SUBJECT  C.  JAN.  25.  1916.  MASK 

50  Gms.  LEVULOSE  IN  1000  c.  c.  NaCl  SOLUTION 


84 


Fig.  83. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  C,  February  15,  1916, 
before  and  after  rectal  injection  of  37.5  grams  of  levulose  in  750  c.  c.  of  a  0.6  per  cent  solu¬ 
tion  of  sodium  chloride.  (Mask,  with  continuous  observation.) 

Fig.  84. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  C,  January  25,  1916, 
before  and  after  rectal  injection  of  50  grams  of  levulose  in  1,000  c.  c.  of  a  0.6  per  cent  solu¬ 
tion  of  sodium  chloride.  (Mask,  with  continuous  observation.) 


SUBJECT  A.  JAN.  15.  1916. 

50  Gms.  LEVULOSE  IN  500  c.  c.  NaCl  SOLUTION  MASK 


SUBJECT  Q  JAN  28.  1916.  MASK 

'50  Gms.  LEVULOSE  IN  1000  c.c.NaCI  SOLUTION 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN  HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 

85  86 


Fig.  85. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  D,  January  28,  1916, 
before  and  after  rectal  injection  of  50  grams  of  levulose  in  1,000  c.  c.  of  a  0.6  per  cent  solution 
of  sodium  chloride.  (Mask,  with  continuous  observation.) 

Fig.  86. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of  subject  A,  January  15,  1916, 
before  and  after  rectal  injection  of  50  grams  of  levulose  in  500  c.  c.  of  a  0.6  per  cent  solution 
of  sodium  chloride.  (Mask,  with  continuous  observation.) 


was  206  c.  c.,  the  latter  value  is  somewhat  high  for  this  subject.  He  had  a 
slight  cold  on  the  evening  of  January  18.  The  preliminary  values  for  C 
ranged  from  265  to  286  c.  c.  His  basal  oxygen  absorption  was  285  c.  c.  The 


154 


HUMAN  METABOLISM  WITH  ENEMATA. 


preliminary  oxygen  data  for  D  were  on  February  11,  209  c.  c. ;  on  February  3, 
222  c.  c.;  and  on  January  28,  215  c.  c. 


SUBJECT  A.  JAN.  18.  1916. 

50  Gms.  LEVULOSE  IN  500  c.c.NaCI  SOLUTION  MASK 


Fig.  87. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of 
subject  A,  January  18,  1916,  before  and  after  rectal  injection  of  50 
grams  of  levulose  in  500  c.  c.  of  a  0.6  per  cent  solution  of  sodium 
chloride.  (Mask,  with  continuous  observation.) 


SUBJECT  C.  JAN.  12.  1916. 

50  Gms.  LEVULOSE  IN  500  c.  c.  NaCl  SOLUTION  MASK 


Fig.  88. — Respiratory  quotient,  oxygen  absorption,  and  pulse- 
rate  of  subject  C,  January  12,  1916,  before  and  after 
rectal  injection  of  50  grams  of  levulose  in  500  c.  c.  of  a 
0.6  per  cent  solution  of  sodium  chloride.  (Mask,  with 
continuous  observation.) 

Respiratory  Quotient. 

The  respiratory  quotients  for  A  in  the  preliminary  periods  were  0.78  on 
January  15  and  0.77  on  January  18.  Those  for  C  ranged  from  0.75  on 
February  15  to  0.82  on  January  12.  The  values  for  D  were  0.80  on  Janu- 


RESPIRATORY  EXCHANGE  WITH  LEYULOSE. 


155 


ary  28  and  0.76  on  February  3  and  February  11.  The  range  for  all  the 
averages  of  pulse-rate,  oxygen  absorption,  and  respiratory  quotient  in  the 
pre-injection  periods  were  well  within  the  range  of  results  obtained  in  the 
basal  metabolism  measurements,  with  the  exception  of  those  with  A  on 
January  18,  in  which  the  pulse-rate  (70  beats)  and  oxygen  absorption  (223 
c.  c.)  were  higher  than  usual. 

Results  of  Measurements  After  Rectal  Injection  of  Levulose. 

The  results  of  these  studies  of  the  respiratory  exchange  after  the  rectal 
injection  of  a  levulose  solution  are  not  readily  interpreted,  as  they  were 
comparatively  few  in  number  and  the  conditions  varied  somewhat.  A  com¬ 
plete  record  of  the  amount  of  sleep  or  drowsiness  in  the  experiments  was  also 
lacking.  While  in  a  number  of  the  observations  the  introduction  of  the 
solution  produced  no  subjective  effects,  in  others  the  men  had  cramps  and 
peristaltic  movements  which  may  have  had  a  relation  to  the  changes  which 
followed  the  injection. 

In  the  first  four  experiments,  those  with  the  introduction  of  25  grams  of 
levulose  in  500  c.  c.  of  a  0.6  per  cent  solution  of  sodium  chloride,  no  cramps 
or  peristaltic  movements  were  reported.  In  the  experiment  with  subject  C 
on  February  15,  1916,  when  37.5  grams  were  given  in  a  volume  of  750  c.  c., 
there  was  some  pain  when  the  final  flushing  of  the  rectum  and  colon  was 
given.  In  an  experiment  with  50  grams  of  levulose  in  a  volume  of  1,000 
c.  c.,  the  same  subject  reported  a  few  peristaltic  movements  near  the  end 
of  the  experiment,  and  subject  D,  with  a  like  injection,  suffered  from  cramps 
for  most  of  the  experimental  period.  When  50  grams  of  levulose  were  given 
in  a  volume  of  500  c.  c.,  subject  A  on  January  15  reported  an  intense  desire 
to  defecate  during  the  experiment,  and  on  January  12  subject  C  had  some 
peristaltic  movement.  Subject  A  on  January  18  complained  that  the 
solution  was  administered  too  rapidly,  although  it  was  given  more  slowly 
than  usual;  also  that  he  suffered  from  cramps  during  the  last  hour  of  the 
observations. 

Owing  to  the  absence  of  sleep  records  in  many  of  the  experiments,  it  is 
not  easy  to  discriminate  between  the  effect  of  levulose  upon  the  pulse-rate 
and  the  effect  of  sleep.  That  the  pulse-rate  was  definitely  affected  by  sleep 
is  particularly  evident  in  the  experiment  with  subject  D  on  February  11, 
for  this  subject  has  normally  a  very  high  pulse-rate  when  he  is  awake. 
There  are,  however,  some  indications  that  the  pulse-rate  was  raised  by  the 
injection  of  the  levulose  solution,  expecially  in  the  experiments  with  subject 
C,  when  the  pulse-rate  in  every  instance  rose  within  1  to  1|  hours  after  the 
beginning  of  the  injection,  and  was  higher  at  this  time  than  in  the  first  hour 
after  the  injection  commenced;  the  comparison  is  therefore  not  dependent 
upon  the  values  for  the  preliminary  period.  This  change  occurred  even  in 
the  experiments  with  25  grams  of  levulose  in  which  there  were  no  cramps  or 
peristaltic  movements. 

In  the  four  experiments  with  25  grams  of  levulose  and  a  volume  of  500 
c.  c.,  there  was  very  little  indication  of  the  effect  of  the  injection  upon  the 
respiratory  quotient,  except  possibly  in  the  experiment  with  subject  D  on 
February  11  in  the  fourth  half  hour  after  the  injection  began,  when  there 
was  an  increase  of  about  0.03.  The  absorption  of  the  levulose  in  these  four 
experiments  was  smaller  than  that  in  the  other  experiments  with  37.5  and  50 


156 


HUMAN  METABOLISM  WITH  ENEMATA. 


grams  of  levulose,  varying  from  16.2  grams  to  21.8  grams.  (See  table  6, 
p.  35.) 

In  the  single  experiment  with  37.5  grams  and  a  volume  of  750  c.  c.,  in 
which  there  was  an  apparent  absorption  of  35.8  grams,  the  respiratory 
quotient  changed  to  a  higher  level  during  the  second  half  hour  after  the 
beginning  of  the  injection,  and  this  level  was  maintained  throughout  the 
rest  of  the  experiment,  although  the  subject  was  slightly  drowsy  near  the  end. 

In  the  two  experiments  on  January  25  and  28  with  50  grams  of  levulose 
and  a  volume  of  1,000  c.  c.,  there  was  apparently  no  change  in  the  quotients 
due  to  levulose.  There  were  cramps  in  both  experiments  and  a  large  absorp¬ 
tion  of  levulose,  i.  e.,  33  and  25.9  grams,  respectively. 

In  the  three  experiments  with  50  grams  and  a  volume  of  500  c.  c.,  the  most 
marked  change  was  found  with  subject  A  on  January  18,  when  the  average 
quotient  rose  from  0.78  to  0.95,  and  there  was  an  apparent  absorption  of  100 
per  cent  of  the  levulose.  It  will  be  remembered  that  on  this  day  the  subject 
complained  of  cramps,  especially  during  the  last  hour,  though  the  maximum 
quotient  did  not  occur  at  this  time.  The  emotional  disturbance  due  to 
cramps  may  have  caused  an  increase  in  respiration,  and  consequently  some 
excessive  elimination  of  carbon  dioxide,  i.  e.,  a  “  washing-out/’  and  thus 
have  raised  the  respiratory  quotient.  One  must  bear  this  in  mind  when 
interpreting  the  results. 

In  the  experiment  with  the  same  subject  on  January  15,  the  effect  was 
somewhat  complicated  by  the  irregularity  of  respiration  due  to  coughing. 
There  may  have  been  here,  also,  a  slight  increase  in  ventilation  as  a  result 
of  the  coughing,  with  a  consequent  increase  in  elimination  of  carbon  dioxide 
which  would  raise  the  respiratory  quotient.  There  was  in  this  experiment 
a  definite  rise  in  the  respiratory  quotient. 

The  duration  of  the  experiment  seemed  to  bear  no  relation  to  the  effect 
upon  the  respiratory  quotient,  as  the  observations  after  the  beginning  of  the 
injection  varied  from  2  hours  and  9  minutes  to  4  hours  and  20  minutes. 
Only  in  the  longest  observation  was  there  much  of  a  change  in  the  quotient 
after  2  hours.  We  thus  see  that  but  a  single  experiment  (that  with  subject 
A  on  January  18)  indicated  a  considerable  increase  in  the  respiratory  quo¬ 
tient  due  to  the  rectal  injection  of  levulose,  and  the  absorption  of  the  sugar  in 
this  case  was  practically  100  per  cent.  Even  in  this  experiment  there  was 
the  complicating  factor  of  cramps. 

The  oxygen  absorption  in  most  of  the  experiments  gives  generally  negative 
evidence  as  to  the  influence  of  the  levulose  injection.  While  there  were 
marked  variations  in  this  factor,  they  were  doubtless  due  more  especially 
to  momentary  excitement  or  to  drowsiness  and  sleep.  The  influence  of  the 
latter  is  definitely  shown  in  the  experiment  with  subject  D  on  Februa^  11 
and  to  some  extent  in  the  experiment  with  subject  C  on  February  15.  The 
marked  variations  in  the  experiment  with  subject  A  on  January  15  resulted 
from  the  uneven  respiration  during  periods  of  coughing. 

Discussion  of  Composite  Chart,  and  Conclusions. 

A  composite  chart  for  the  levulose  experiments  is  given  in  figure  89, 
and  includes  all  the  experiments  which  were  made  with  levulose,  i.  e.,  those 
with  both  5  per  cent  and  10  per  cent  solutions  containing  25  to  50  grams 
of  levulose. 


RESPIRATORY  EXCHANGE  WITH  ORAL  INGESTION  OF  SUGARS.  157 


Pulse-rate. — The  curve  for  the  pulse-rate  rises  slightly  during  the  first 
1|  hours  after  the  injection  and  then  falls  during  the  fourth  hour  nearly  to 
the  preliminary  value.  The  rise  in  the  pulse-rate  was  therefore  of  short 
duration  and  not  very  marked. 

Oxygen  absorption. — In  the  oxygen  curve  there  is  a  slight  rise  which  be¬ 
gins  immediately,  continues  throughout  the  preliminary  period,  and  prac¬ 
tically  ceases  by  the  end  of  the  first  half  hour  after  injection.  It  is  probable 
that  the  levulose  had  no  share  in  increasing  the  oxygen  absorption  in  this 
first  half  hour  after  the  injection. 

Respiratory  quotient. — The  course  of  the  respiratory  quotient  is  somewhat 
peculiar  in  that  there  is  a  rise  during  the  preliminary  period  nearly  to  0.80 
from  0.77.  It  then  drops  during  the  first  hour  after  injection  almost  to  the 
level  at  the  beginning  of  the  preliminary  period,  and  subsequently  rises  until, 
during  the  third  hour  after  injection,  it  averages  0.83.  This  is  about  0.05 
above  the  lowest  quotient  during  the  hour  after  injection  and  the  lowest 
point  before  injection.  This  average  is  influenced  to  some  extent  by  one  or 
two  experiments  in  which  there  was  a  marked  rise  in  the  respiratory 
quotient. 


Fig.  89. — Chart  showing  compo¬ 
site  results  for  measurements 
of  respiratory  quotient,  oxy¬ 
gen  absorption,  and  pulse-rate 
in  10  experiments  with  rectal 
injection  of  25  to  50  grams  of 
levulose  in  5  and  10  per  cent 
solutions.  (Mask.) 


COMPOSITE  CHART.  RECTAL  INJECTION  OF  LEVULOSE  IN  0.6  FER  CENT 


RE 

SPIRATC 

IRV  QU(! 

THENT 

O. 

PER  Ml 

MUTE.c. 

c. 

JLSE  PE 

R  MINU 

rl 

It 

2  3  4  J 

> 

7  8 

250 

225 

200 

75 

70 

65 


HALF  HOURS  AFTER  RECTAL  INJECTION  BEGAN 


In  general,  therefore,  we  may  state  that  the  injection  of  25  to  50  grams  of 
levulose  in  solution  caused  only  a  slight  increase  in  the  respiratory  quotient 
in  the  majority  of  cases;  that  there  was  no  positive  effect  upon  the  oxygen 
consumption;  and  that  the  levulose  evidently  increased  the  pulse-rate 
somewhat  in  individual  cases. 

RESPIRATORY  EXCHANGE  WITH  ORAL  INGESTION  OF 

SUGARS. 

The  respiratory  exchange  with  man  after  the  ingestion  by  mouth  of 
dextrose  or  levulose  has  been  studied  by  Durig,1  Benedict  and  Carpenter,2 
and  Higgins,3  using  100-gram  quantities.  These  investigators  found  almost 
immediate  and  striking  increases  in  the  respiratory  quotient  and  the  two 
former  found  increases  in  the  metabolism  after  the  ingestion  of  levulose. 

1  Togel,  Brezina,  and  Durig:  Biochem.  Zeitschr.,  1913,  50,  p.  296. 

*  Benedict  and  Carpenter:  Carnegie  Inst.  Wash.  Pub.  No.  261,  1918,  p.  171. 

3  Higgins:  Am.  Jour.  Physiol.,  1916,  41,  p.  258. 


158 


HUMAN  METABOLISM  WITH  ENEMATA. 


The  rise  both  in  quotient  and  total  metabolism  was  less  marked  after  the 
ingestion  of  dextrose  and  did  not  appear  so  promptly  as  with  levulose.  It 
was  planned  in  this  research  to  include  a  series  of  experiments  with  oral 
introduction  of  levulose  and  dextrose,  using  the  same  quantities  and  dilu¬ 
tions  as  in  the  rectal  feeding  experiments,  these  being  much  smaller  than 
those  usually  employed  for  mouth  experiments.  Only  two  observations 
were  completed  under  these  conditions,  i.  e.,  one  each  with  dextrose  and 
levulose.  These  are  reported  here,  and  while  we  must  not  draw  fixed 
conclusions  from  single  experiments,  the  results  are  quite  in  line  with  previ¬ 
ous  work  on  dextrose  and  levulose  and  therefore  can  serve  as  a  basis  of 
contrast  with  results  obtained  in  rectal  feeding. 

Subject  C,  April  lj,  1917. — Ingestion  by  mouth,  30  grams  dextrose  in  500 
c.  c.  water.  The  results  are  shown  graphically  in  figure  90.  While  several 
short  periods  of  sleep  produced  rather  marked  variations  in  all  three  factors, 
the  general  result  of  the  ingestion  of  this  amount  of  dextrose  was  to  increase 
the  quotient  to  approximately  0.90  at  about  the  third  half  hour  after  ingestion, 
with  a  subsequent  fall  in  2  hours  to  nearly  the  preliminary  level  of  0.79. 
There  was  no  change  in  oxygen  absorption  other  than  that  due  to  activity,  and 
no  change  in  pulse-rate  which  can  be  ascribed  to  the  dextrose  solution. 


Fig.  90. — Respiratory  quotient, 
oxygen  absorption,  and  pulse- 
rate  of  subject  C,  April  14,  1917, 
before  and  after  oral  ingestion  of 
30  grams  of  dextrose  in  500  c.  c. 
of  distilled  water.  (Mask,  with 
continuous  observation.) 


SUBJECT  C  APR.  14.  t917 

30  Gms.  DEXTROSE  IN  500  c.o.  WATER  BY  MOUTH  MASK 


Subject  C,  April  20,  1917. — Ingestion  by  mouth,  30  grams  levulose  in  500 
c.  c.  water.  The  results  are  given  in  figure  91.  There  was  but  one  short  pe¬ 
riod  of  sleep  at  the  end  of  the  second  half  hour  after  ingestion.  The  respiratory 
quotient  changed  from  an  average  of  0.81  in  the  preliminary  period  to  a  max¬ 
imum  of  0.98  in  less  than  an  hour  after  ingestion,  then  gradually  fell  to  nearly 
the  preliminary  level  in  3  hours  after  ingestion.  The  general  level  of  the 
curve  for  the  oxygen  absorption  is  slightly  higher  after  the  levulose  than 
that  for  the  preliminary  values,  which  is  also  true  for  the  pulse-rate. 

While  the  results  of  these  two  experiments  are  quite  in  line  with  those 
obtained  with  larger  quantities  in  earlier  work,  they  are  somewhat  different 


PRACTICAL  CONSIDERATIONS. 


159 


from  the  findings  with  the  rectal  injection  of  the  same  substances  in  like 
quantities  (see  pp.  150  and  155),  for  with  mouth  feeding  the  greater  change 
in  the  respiratory  quotient  was  produced  with  levulose,  whereas  with  rectal 
feeding  the  more  definite  alteration  in  the  same  factor  was  found  with  dex¬ 
trose.  The  relationship  between  oral  and  rectal  feeding  will  be  discussed 
more  completely  in  the  following  section. 


SUBJECT  a  APR.  2Q  1917 

30  Gma.  LEVULOSE  IN  500  o.c.  WATER  BY  MOUTH  MASK 


Fig.  91. — Respiratory  quotient,  oxygen  absorption,  and  pulse-rate  of 
subject  C,  April  20,  1917,  before  and  after  oral  ingestion  of  30 
grams  of  levulose  in  500  c.  c.  of  distilled  water.  (Mask,  with 
continuous  observation.) 

GENERAL  DISCUSSION  OF  RESULTS. 

PRACTICAL  CONSIDERATIONS. 

The  chief  purpose  of  this  investigation  was  the  study  of  the  metabolism 
with  rectal  injection  of  various  substances.  It  was  therefore  not  primarily  a 
clinical  study,  and  consequently  its  value  as  a  clinical  contribution  is  not  of 
chief  importance.  There  are,  however,  a  number  of  practical  points  as  to 
the  clinical  use  of  rectal  feeding  which  may  be  considered  in  the  light  of  the 
experience  which  has  been  obtained  in  these  experiments.  The  chief  ob¬ 
jections  to  giving  nutriment  by  rectum  are  the  discomfort  to  the  patient  and 
the  fact  that  the  injections  can  not  be  continued  very  long.  It  is  therefore 
advisable  to  consider  the  subjective  impressions  of  the  individuals  who 
underwent  these  experimental  conditions  to  find  if  they  have  practical  value 
in  clinical  work. 


Temperature  of  Material  Injected. 

One  prominent  feature  of  the  reports  made  by  the  subjects  was  the  state¬ 
ment  that  the  liquid  felt  cool,  notwithstanding  the  fact  that  the  solutions 
when  placed  in  the  container  were  generally  at  or  about  body-temperature, 
i.  e.,  from  37°  to  40°  C. ;  in  one  case  the  temperature  of  the  solution  was  45°  C. 
The  container  was  a  glass  leveling-bulb  of  sufficient  size  to  hold  a  liter  or 


160 


HUMAN  METABOLISM  WITH  ENEMATA. 


more  of  the  enema.  From  the  container  the  solution  usually  ran  down 
through  a  rubber  tube  into  a  catheter  and  thence  into  the  rectum  of  the  sub¬ 
ject;  the  solution  thus  had  an  opportunity  to  cool  before  reaching  the  man’s 
body. 

The  drop  method  described  by  Murphy* 1  necessitates  the  use  of  an  electric 
warming-tube  at  or  near  the  entrance  of  the  catheter.  Various  methods 
have  been  suggested  for  keeping  the  solution  warm,  such  as  hot  sand-bags, 
hot-water  bottles,  and  similar  devices.  Kemp2  discusses  the  temperature  of 
enemas,  the  highest  considered  being  120°  F.  In  this  connection  he  pub¬ 
lishes  a  table  showing  that  when  the  temperature  of  the  water  in  the  con¬ 
tainer  is  193°  F.,  the  temperature  of  the  liquid  as  it  finally  reaches  the  rec¬ 
tum  is  only  115°  F.,  the  difference  in  temperatures  being  dependent  upon  the 
number  of  drops  entering  the  bulb  per  minute,  the  length  of  the  rubber  tub¬ 
ing,  and  the  environmental  temperature.  Water  with  a  temperature  in  the 
container  of  115°  F.  will  enter  the  rectum  at  the  same  temperature  when 
flowing  at  the  rate  of  200  drops  per  minute.  This  rate  of  flow  is  somewhat 
faster  than  that  ordinarily  used  in  the  Nutrition  Laboratory  with  the  drop 
method,  the  rate  generally  employed  here  being  about  1  drop  per  second, 
that  is,  60  drops  per  minute. 

On  the  general  principle  that  physical  and  chemical  reactions  proceed  fast¬ 
er  at  the  higher  temperatures,  it  is  desirable  to  have  the  solution  as  warm  as 
possible  without  danger  of  injuring  the  lining  of  the  colon;  at  least,  the  solu¬ 
tions  should  not  be  cold,  as  this  is  liable  to  cause  a  high  tonic  condition,  with 
consequent  peristalsis.  Warmth  tends  to  produce  relaxation,  which  is  de¬ 
sirable  in  rectal  feeding,  as  the  one  thing  to  avoid  is  a  tonic  condition. 
Olschanetzky3  studied  the  time  of  appearance  in  the  urine  and  saliva  of  the 
reaction  for  iodine  after  rectal  injection  of  potassium  iodide.  He  found  that 
the  warmer  the  solution  was  when  injected,  the  sooner  the  reaction  took 
place.  He  also  studied  the  time  of  disappearance  of  the  reaction  and  found 
with  lithium  carbonate  that  it  was  from  44  to  48  hours  when  the  solution 
was  injected  cold.  When  injected  at  25°  C.,  it  disappeared  in  44  hours,  at 
35°  C.  in  24  hours,  and  at  40°  and  45°  C.  in  20  hours.  Thus,  the  time  of  ap¬ 
pearance  and  the  rate  of  elimination  of  these  substances  were  influenced  by 
the  temperature  of  the  solution  when  injected. 

Rate  of  Flow. 

In  the  experiments  in  this  research,  the  rate  of  injection  varied  from  265 
c.  c.  in  1  minute  to  1,000  c.  c.  in  several  hours.  Other  things  being  equal,  the 
slower  rates  of  flow  are  the  more  desirable,  as  the  possibility  of  sensation  by 
the  subject  is  thus  avoided  or  diminished.  If  the  solution  is  introduced 
rapidly  at  first,  the  amount  of  sensation  felt  by  the  subject  is  out  of  propor¬ 
tion  to  the  amount  of  solution  introduced.  The  threshold  for  sensation, 
that  is,  the  amount  introduced  per  minute  sufficient  for  the  subject  to  be 
conscious  of  it,  may  at  first  be  low.  After  the  flow  has  started,  the  rate  may 
be  increased,  with  less  probability  that  the  subject  will  realize  the  change. 
Apparently,  this  sensation  as  to  rate  of  flow  varied  at  times,  because  in  a 
number  of  cases  the  subjects  reported  that  they  thought  the  solution  was 

1  Murphy:  Jour.  Am.  Med.  Assoc.,  1909,  52,  p.  1248. 

1  Kemp:  Handbook  of  Medical  Sciences,  1914,  4,  p.  40. 

*  Olschanetzky:  Deutsch.  Arch.  f.  klin.  Med.,  1890,  48,  p.  619. 


PRACTICAL  CONSIDERATIONS. 


161 


flowing  very  rapidly  when,  as  a  matter  of  fact,  it  was  being  introduced  at  a 
rate  of  not  more  than  one  drop  per  second. 

The  consciousness  of  the  passage  of  the  liquid  into  the  rectum  is  also  de¬ 
pendent  to  a  certain  extent  upon  the  temperature  of  the  solution.  When  the 
liquid  is  cold,  its  passage  is  felt  more  quickly  than  when  it  is  introduced  at  or 
about  body-temperature,  as  in  the  latter  case  the  only  sensation  would  be  the 
mechanical  effect  of  its  introduction  rather  than  the  double  sensation  of  the 
rate  of  flow  and  the  difference  between  the  temperature  of  the  body  and  that 
of  the  solution.  We  have  found  that  the  drop  method  is  most  satisfactory 
when  volumes  larger  than  250  c.  c.  are  to  be  introduced.  The  drop  method 
has  but  one  disadvantage,  namely,  that  previously  stated,  that  the  solutions 
may  cool  considerably  between  the  time  they  are  prepared  and  the  time  that 
they  reach  the  colon.  One  advantage  of  the  drop  method  is  that  there  is  less 
liability  of  a  large  and  sudden  accumulation  in  volume,  with  consequent  in¬ 
crease  in  pressure;  also,  when  concentrated  solutions  are  used  with  this 
method,  there  is  less  danger  of  peristalsis  and  cramps. 

A  method  for  avoiding  difficulty  due  to  sudden  changes  in  volume  and  one 
which  requires  very  little  attention  to  the  introduction  of  the  liquid  has  been 
proposed  by  McClanahan.1  During  medical  attendance  in  the  Virgin  Is¬ 
lands  he  did  not  have  adequate  assistance,  and  so  arranged  that  the  container 
and  tubing  should  be  set  at  a  level  at  or  about  the  height  at  which  the  tube 
entered  the  rectum.  He  claims  that  in  this  way  there  can  be  no  pressure  due 
to  accumulation,  and  if  peristalsis  begins  the  solution  goes  back  into  the  con¬ 
tainer.  The  whole  matter  of  feeding  is  automatically  taken  care  of  by  plac¬ 
ing  the  container  but  slightly  above  the  level  of  the  body. 

Volume  of  Injection. 

Most  of  the  recommendations  for  rectal  feeding  suggest  a  volume  for  the 
injection  of  250  to  500  c.  c.,  and  these  two  volumes  represent  those  which  are 
actually  practical.  Other  things  being  equal,  a  volume  of  250  c.  c.  is  prefer¬ 
able  because  there  is  less  danger  of  accumulation  and  pressure,  with  peristal¬ 
sis  as  a  result.  In  a  number  of  cases  in  this  research,  1,000  c.  c.  were  given  in 
a  short  period  of  time,  but  this  caused  cramps  and  increased  pressure  which 
was  greater  than  desirable.  It  is  better  to  give  small  volumes  intermittently 
rather  than  to  attempt  the  injection  of  a  considerable  volume  in  a  short  pe¬ 
riod  of  time. 

Maximum  Time  of  Retention. 

In  the  observations  here  made  there  is  no  attempt  to  determine  the  ulti¬ 
mate  time  so  far  as  retention  was  concerned.  It  has  been  brought  out  in  the 
literature  and  also  in  our  own  experiments  that  apparently  the  greater  part  of 
the  absorption  takes  place  in  the  first  2  hours;  consequently,  when  it  is  de¬ 
sired  to  inject  as  much  as  possible  there  will  be  but  little  gained  by  waiting 
longer  than  2  hours  before  a  second  injection  is  given,  as  the  additional  ab¬ 
sorption  which  may  take  place  from  a  5  or  10  per  cent  solution  is  not  great 
enough  to  warrant  extending  the  period  of  absorption.  Whether  or  not  the 
absorbed  liquid  should  be  removed  before  a  second  injection  is  given  is  not 
determined  by  these  studies.  In  fact,  it  might  be  possible  to  give  a  second 
injection  in  an  even  shorter  period  of  time  than  2  hours.  We  have  no  data 


1  McClanahan:  Jour.  Am.  Med.  Assoc.,  1921,  76,  p.  174. 


162 


HUMAN  METABOLISM  WITH  ENEMATA. 


on  this  particular  point,  but  it  is  a  feature  of  rectal  injection  which  must  be 
considered  when  as  much  material  as  possible  must  be  introduced  in  a  short 
space  of  time. 

Position  of  Subject  During  Injection. 

In  the  majority  of  the  experiments,  the  injection  was  given  with  the 
subject  lying  on  his  back,  although  it  is  generally  recommended  that  the 
subject  should  lie  on  his  right  side,  in  the  so-called  ‘ ‘knee-chest”  position. 
According  to  Cannon,1  the  matter  of  gravity  plays  but  little  role  in  the  ques¬ 
tion  of  digestion  and  absorption  in  the  alimentary  tract.  The  suggestion 
that  with  the  subject  lying  on  the  right  side,  the  solution  will  reach  the 
transverse  colon  and  pass  into  the  ascending  colon  has  therefore  but  little 
practical  value.  Case  2  says  that  the  “  knee-chest  position  for  enemas  is 
quite  unnecessary,  for  unless  there  is  some  growth  or  obstruction,  the  colon 
fills  easily  when  the  patient  lies  supine.’ 7  In  several  of  the  experiments  in 
this  research,  the  subject  was  in  the  sitting  position,  but  this  attitude  is 
apparently  not  so  favorable  for  rectal  feeding  as  that  with  the  subject  lying 
on  his  back. 

That  the  supine  position  is  most  favorable  is  also  shown  by  the  fact  that 
the  pressure  in  the  tubing  was  much  less  when  the  subject  was  lying  on  his 
back  than  when  he  was  sitting.  Indeed,  it  would  seem  desirable  to  employ 
a  pressure  indicator  of  some  kind  in  rectal  feeding.  With  one  subject, 
1,000  c.  c.  were  given  in  a  little  over  2  hours;  cramps  and  intense  peristalsis 
developed  and  the  back-pressure,  i.  e.,  the  height  to  which  the  solution  rose 
in  the  tubing  when  no  feeding  was  taking  place,  was  34  cm.,  the  column  of 
the  solution  rising  and  falling  with  the  respiration.  In  many  cases  when  the 
subject  was  lying  on  his  back,  the  pressure  was  never  more  than  10  cm., 
even  though  the  solution  was  fed  rapidly,  and  frequently  there  was  entire 
absence  of  pressure  in  the  tubing.  Joltrain,  Baufle,  and  Coope  3  describe 
an  instrument  (a  telenteromanometer)  for  measuring  the  colonic  pressure, 
but  this  was  devised  after  the  present  research  had  been  made. 

Use  of  Sodium  Chloride. 

It  is  customary  with  any  solution  which  is  to  be  retained  and  absorbed  to 
include  sodium  chloride  in  a  concentration  of  0.6  per  cent,  that  is,  a  solution 
isotonic  with  the  blood.  Such  addition  does  not  appear  to  be  necessary, 
for  unless  the  body  needs  sodium  chloride  it  does  not  seem  desirable  to 
increase  the  amount  to  be  absorbed,  particularly  as  with  material  intro¬ 
duced  by  mouth  no  effort  is  made  to  use  isotonic  solutions  or  to  add  sodium 
chloride  in  such  quantity  as  to  make  the  solution  isotonic  with  the  blood. 
Logically,  to  secure  a  proper  solution  for  rectal  injection,  one  should  like¬ 
wise  add  all  of  the  other  constituents  which  are  inorganic  and  isotonic  with 
the  blood.  When  the  body  has  been  actually  dehydrated  it  may  be  desirable 
to  add  distilled  water  rather  than  to  give  a  solution  containing  inorganic 
constituents. 

1  Cannon:  The  mechanical  factors  of  digestion,  New  York,  1911,  p.  48. 

2  Case".  Medical  Clinics  of  Chicago,  January,  1917,  2,  p.  830. 

‘Joltrain,  Baufle,  and  Coope:  Bull,  de  la  Soc.  Med.  des  Hopitaux,  Paris,  1919,  43,  p.  211. 


PRACTICAL  CONSIDERATIONS. 


163 


Addition  of  Opium. 

In  a  number  of  the  experiments,  that  is  those  with  the  sugars,  5  to 
10  drops  of  tincture  of  opium  were  added.  This  procedure  is  almost  uni¬ 
versally  recommended  for  the  purpose  of  preventing  peristalsis  or  pain. 
There  is  no  evidence  in  the  experiments  of  this  research  that  the  addition  of 
tincture  of  opium  was  either  beneficial  or  disadvantageous.  Leubuscher  1 
studied  the  effect  of  different  substances  upon  intestinal  absorption.  He 
injected  in  similar  loops  of  intestine  solutions  of  potassium  iodide  or  of 
dextrose  with  and  without  drugs.  The  addition  of  morphine  or  opium  low¬ 
ered  the  absorption  about  one-fourth  or  one-third.  The  addition  of  0.5 
to  2.0  per  cent  of  alcohol  caused  an  increase  with  potassium-iodide  solution, 
while  4  to  10  per  cent  depressed  the  absorption.  The  0.5  to  1.0  per  cent  of 
alcohol  caused  an  increase  in  the  absorption  of  dextrose,  while  with  2  per 
cent  the  absorption  usually  was  less  than  from  water  solution  alone. 

While  the  use  of  opium  is  commonly  recommended,  it  would  seem  more 
logical  to  give  attention  to  eliminating  conditions  which  induce  peristalsis, 
such  as  cold  solutions,  large  volumes,  and  anxiety  on  the  part  of  the  subject, 
rather  than  to  add  an  inhibiting  drug  which,  though  possibly  a  preventive 
of  peristalsis,  would  at  the  same  time  lower  the  rate  of  absorption. 

Removal  of  Unabsorbed  Material. 

The  chief  difficulty  in  determining  the  absorption  in  rectal  feeding  is  the 
fact  that  the  cleansing  enema,  or  wash-out,  taken  at  the  end  of  the  observa¬ 
tion  in  rectal  feeding  experiments,  does  not  remove  all  of  the  substance  un¬ 
absorbed.  Very  few  studies  have  been  made  to  determine  whether  a  second 
wash-out  removes  additional  material.  Schoenborn 2  used  500  c.  c.  of 
water  for  his  first  wash-out  and,  in  order  to  prove  that  this  removed  all  the 
unabsorbed  sugar,  he  gave  a  second  and  reports  that  he  never  found  sugar 
in  the  material  from  the  second  wash-out.  Bergmark  3  usually  had  first  a 
defecation,  and  then  two  wash-outs  of  250  c.  c.  each,  and  tested  the  material 
obtained  for  sugar.  He  reported  that  the  second  wash-out  always  gave 
negative  results. 

In  the  experimental  work  here  recorded,  it  is  shown  that,  in  general,  there 
was  some  unabsorbed  material  not  washed  out  after  the  first  enema  was 
given  at  the  end  of  the  observation.  On  the  other  hand,  there  were  several 
experiments  in  which  no  material  remained  in  the  rectum,  or  in  which  the 
quantity  obtained  in  the  second  wash-out  was  so  small  as  to  be  of  no  sig¬ 
nificance.  There  is  great  need  for  a  substance  that  can  be  introduced  that 
will  not  be  absorbed,  but  whose  quantity  can  be  determined  accurately  by 
chemical  or  physical  means,  so  that  we  may  find  (1)  whether  a  first  wash¬ 
out  removes  all  of  the  unabsorbed  material;  (2)  whether  the  size  of  the  wash¬ 
out  makes  any  difference;  and  (3)  whether  any  of  the  material  passes  by 
the  ileocecal  valve. 

That  the  solutions  actually  passed  well  up  into  the 'colon  is  confirmed  by 
the  fact  that  the  subjects  reported  feeling  its  passage  across  the  abdomen 

1  Leubuscher:  Verhandl.  des  Cong.  f.  inn.  Med.,  1890,  p.  436. 

2  Schoenborn:  Zur  Frage  der  Resorption  von  Kohlehydraten  im  menschlichen  Rectum.  Diss., 

Wurzburg,  1897. 

*  Bergmark:  Skand.  Arch.  f.  Physiol.,  1915,  32,  p.  355. 


164 


HUMAN  METABOLISM  WITH  ENEMATA. 


and  down  the  right  side,  and  Cannon  and  Case  have  each  shown  that  solu¬ 
tions  have  passed  both  into  the  colon  and  into  the  cecum.  The  passage  of 
material  through  the  ileocecal  valve  is  more  of  theoretical  than  of  practical 
importance.  If  it  is  desired  to  administer  materials  rectally,  it  is  of  little 
significance  whether  the  substance  passes  into  the  body  through  the  ileocecal 
valve  or  whether  it  is  absorbed  in  the  colon.  But  when  one  is  studying  the 
effect  of  introducing  substances  rectally  with  special  reference  to  absorption 
from  the  colon  and  its  further  paths  into  the  body,  it  is  of  special  importance 
that  one  should  know  whether  it  does  or  does  not  pass  the  ileocecal  valve. 
In  a  number  of  investigations  this  difficulty  has  been  overcome  by  using 
various  mechanical  contrivances  to  prevent  its  passage  through  the  valve. 
In  one  instance,  a  heavy  weight  or  pressure  was  put  upon  the  right  side  to 
prevent  material  from  passing  by.  In  several  studies  (see  pp.  3  and  7),  a 
distensible  balloon  or  tampon  was  inserted  far  enough  into  the  rectum  to 
close  off  a  short  length  of  the  lower  part  of  the  intestine  and  make  it  available 
for  the  absorption  of  injected  solutions.  With  animals,  operations  have 
been  performed  in  which  the  ileocecal  valve  has  actually  been  tied  off,  so 
as  to  make  sure  that  no  material  passed  by  it. 

Studies  have  likewise  been  made  by  means  of  the  Roentgen  ray,  particu¬ 
larly  by  Case,1  from  which  it  has  been  found  that  the  passage  of  the  material 
through  the  ileocecal  valve  is  somewhat  dependent  upon  the  volume  and 
also  upon  the  pressure  used  in  forcing  it  into  the  colon.  Substances  such  as 
lycopodium  powder  have  also  been  introduced  with  the  idea  of  finding 
whether  they  traveled  up  the  alimentary  tract,  and  they  have  been  found 
in  the  stomach. 

The  volume  of  wash-out  after  injection  should  not  be  less  than  500  c.  c. 
Judging  from  experience  in  these  investigations,  three  of  these  will  remove 
practically  all  of  the  unabsorbed  material  which  can  be  reached  in  this  way. 

For  the  cleansing  enemas  before  the  feeding  is  begun,  it  is  desirable  to  give 
them  in  such  number  and  of  such  size  that  the  colon  will  be  free  from  fecal 
and  unabsorbed  material  before  the  injection.  At  first  this  was  not  so  care¬ 
fully  controlled  in  our  experimental  work,  but  later,  the  subjects  followed 
faithfully  the  instructions  to  use  a  liter  of  warm  water  while  they  were  in  a 
sitting  position  and  to  repeat  this  procedure  until  the  last  wash-out  showed 
practically  no  material  brought  away,  that  is,  the  rejected  liquid  was  practi¬ 
cally  clear.  In  spite  of  this  care,  however,  there  were  instances  in  which 
the  final  wash-out  showed  that  fecal  material  had  apparently  traveled  down 
into  the  large  intestine  and  was  removed  when  the  final  wash-out  was  given. 

SUBJECTIVE  IMPRESSIONS  REGARDING  THE  VARIOUS 

SOLUTIONS. 

Sodium-Chloride  Solutions. 

According  to  the  subjective  impressions  of  the  subjects,  the  solution  of 
sodium  chloride  did  not  cause  peristalsis  or  desire  to  defecate  during  the  time 
of  retention.  In  two  instances,  subject  B  on  October  21,  and  subject  A  on 
March  14,  the  men  reported  after  the  experiment  that  in  one  case  there  was 
diarrhea  and  in  the  other  there  was  a  tendency  for  the  bowels  to  be  irregular 
or  more  frequent  in  movement,  with  a  desire  to  defecate.  The  subjects  in 


1  Case:  Proc.  XVII  International  Cong,  of  Medicine,  London,  1914,  Sect.  Radiology,  p.  1. 


SUBJECTIVE  IMPRESSIONS. 


165 


many  instances  could  not  tell  when  the  solution  was  injected,  this  usually 
being  due  to  the  fact  that  they  were  asleep  at  the  time. 

Alcohol  Solutions. 

The  subjects  had  various  ideas  as  to  the  material  contained  in  the  solu¬ 
tions.  One  man  reported  tasting  alcohol  about  20  minutes  after  an  alcohol 
solution  had  been  injected.  It  was  suggested  to  him  that  he  report  again 
when  he  thought  alcohol  was  given  and  in  one  experiment  when  a  solution 
of  sodium  chloride  was  given  to  him,  he  again  said  he  tasted  alcohol  at  about 
the  same  time  as  before.  Afterwards  he  was  doubtful  as  to  whether  the 
material  given  was  alcohol  and  could  only  say  that  it  had  a  sweetish  taste 
that  lasted  a  long  time. 

5  per  cent  alcohol  solution. —  In  most  of  the  cases  in  which  the  subjects 
received  a  5  per  cent  alcohol  solution,  even  if  it  were  given  when  they  were 
asleep,  on  waking  they  thought,  and  in  some  cases  were  certain,  that  the 
solution  contained  alcohol.  They  could  not  always  give  their  reasons  for 
this  belief,  but  one  subject  reported  that  after  alcohol  there  was  likely  to  be 
some  gas  in  the  colon  which  was  removed  in  the  final  wash-out. 

7.5  per  cent  alcohol  solution. —  Subject  D  reported  tasting  alcohol,  but,  as 
previously  mentioned,  he  also  reported  tasting  it  when  the  solution  of  sodium 
chloride  was  given.  Subject  A  reported  flushing,  perspiration  of  the  feet, 
and  drowsiness  with  a  7.5  per  cent  alcohol  solution.  Subject  A  on  February 
3-4,  1917,  said  on  waking  up  some  time  after  the  injection  that  he  felt  in¬ 
toxicated.  The  same  subject,  however,  a  month  later  reported  that  he 
thought  the  injection  was  a  sodium-chloride  or  sugar  solution,  although  he 
was  still  getting  the  same  quantity  of  alcohol,  namely,  500  c.  c.  of  a  7.5  per 
cent  alcohol  solution. 

10  per  cent  alcohol  solution. — Subjects  A  and  C  reported  with  a  10  per  cent 
alcohol  solution  that  they  believed  that  alcohol  had  been  given  them,  as  they 
felt  warm  and  intoxicated. 

Maximum  alcohol  effect. — The  most  marked  effect  of  giving  alcohol  was 
with  subject  C  on  April  18,  who  received  810  c.  c.  of  a  7.5  per  cent  alcohol 
solution  over  a  duration  of  several  hours.  He  left  the  laboratory  in  the  latter 
part  of  the  afternoon,  went  immediately  to  the  medical  school  near  by, 
smoked,  and  remained  a  half  hour.  He  found  that  his  feet  and  legs  did  not 
seem  to  obey  him,  and  while  his  mind  was  clear  it  was  inclined  to  be  sluggish. 
He  then  went  into  the  city  but  was  very  pale  and  nauseated.  He  was  some¬ 
what  relieved  by  taking  a  cup  of  coffee,  but  had  no  appetite,  with  a  positive 
distaste  for  broth.  He  ate  nothing  until  11  p.  m.  and  then  had  a  light  lunch. 
During  the  night  he  was  sleepless  and  read  until  lh  30m  a.  m.,  but  felt  no 
after  effects  the  next  morning.  The  quantity  he  received  (60  grams)  was 
much  larger  that  in  any  of  the  other  experiments. 

Sugar  Solutions. 

Dextrose. — Of  10  experiments  with  dextrose,  there  were  2  in  which  the 
subjects  reported  cramps,  and  difficulty  of  retention.  Subject  A,  who  re¬ 
ceived  1,000  c.  c.  of  a  solution  containing  60  grams  of  dextrose  on  April  28, 
1916,  reported  periodical  cramps,  but  these  disappeared  when  the  final  enema 
was  taken.  Subject  A  also  reported  cramps  on  February  22, 1917,  and  found 


166 


HUMAN  METABOLISM  WITH  ENEMATA. 


it  difficult  to  remain  quiet.  All  of  the  other  experiments  were  without 
particular  sensations  or  discomfort. 

Levulose. — Subject  C,  in  experiments  on  January  25  and  February  15, 
reported  cramps  and  peristalsis.  Subject  D  on  January  28  had  still  more 
difficulty.  This,  however,  was  due  to  the  conditions  of  the  experiment,  as  he 
was  in  the  sitting  position  and  the  large  volume  of  the  solution  (1,000  c.  c.) 
was  introduced  somewhat  rapidly.  Subject  A  on  January  18  had  cramps, 
and  on  January  15  reported  discomfort  and  a  strong  desire  to  defecate. 

General  Summary  of  Impressions. 

The  subjective  impressions  of  the  men  used  for  this  research  indicate  that 
the  solution  of  sodium  chloride  caused  no  particular  difficulty;  alcohol 
appeared  to  produce  drowsiness,  flushing,  and  unsteadiness  in  a  number  of 
cases;  dextrose  had  no  effect  in  most  of  the  experiments;  and  levulose  caused 
more  distress  and  was  more  difficult  to  retain  than  any  of  the  other  materials 
used  in  this  investigation. 

THEORETICAL  CONSIDERATIONS. 

Utilization  of  Alcohol  in  Rectal  Feeding. 

The  foregoing  sections  give  the  data,  with  summaries,  which  were  obtained 
in  the  study  of  the  rectal  feeding  of  alcohol  and  of  solutions  of  sodium 
chloride,  levulose,  and  dextrose.  The  results  of  these  injections  have  been 
studied  from  the  standpoints  of  absorption  of  the  material  introduced,  the 
effect  upon  flow  of  urine,  the  elimination  of  alcohol  in  the  urine,  the  periodic 
variation  of  the  alcohol  in  the  urine,  the  effect  upon  the  volume  of  urine  and 
some  constituents,  and  the  influence  upon  the  pulse-rate,  the  respiratory 
quotient,  and  the  oxygen  absorption.  It  is  the  purpose  here  to  discuss  the 
evidence  which  these  results  give  of  the  utilization  of  the  different  materials 
which  were  injected  into  the  rectum.  As  most  of  the  study  is  concerned 
with  the  rectal  injection  of  alcohol,  its  utilization,  as  indicated  by  the  results 
obtained  in  the  various  phases  of  the  study,  will  be  discussed  first. 

ABSORPTION  OF  ALCOHOL  AS  AN  INDICATION  OF  UTILIZATION. 

It  is  evident  that  a  substance  will  not  be  utilized  in  the  body  if  it  is  not  ab¬ 
sorbed.  On  the  contrary,  the  fact  that  it  is  absorbed  does  not  indicate  utili¬ 
zation,  even  though  it  is  of  first  importance  that  we  know  whether  or  not  the 
material  is  actually  absorbed.  When  alcohol  is  given  by  mouth  it  is  evi¬ 
dently  utilized,  since  its  excretion  in  the  urine,  breath,  and  through  the  skin 
constitutes  a  very  small  proportion  (under  5  per  cent)  of  the  total  amount 
ingested.  The  absorption  experiments  with  rectal  injection  furnish  evidence 
that  the  material  injected  was  retained  in  the  body.  (See  p.  27.)  In  these 
experiments  a  second  wash-out  was  given  in  a  number  of  instances  to  obtain 
proof  as  to  whether  the  first  wash-out  had  removed  all  of  the  unabsorbed 
material.  It  was  often  found,  when  these  two  wash-outs  were  used,  that 
either  no  alcohol  was  found  in  the  first,  so  that  it  was  unnecessary  to  ana¬ 
lyze  the  material  from  the  second,  or  else  that  when  some  unabsorbed  alco¬ 
hol  was  found  with  the  first  wash-out,  none  was  secured  from  the  second. 

In  two  absorption  experiments  with  a  5  per  cent  alcohol  solution,  namely, 
those  with  A  on  May  16  and  with  C  on  May  13,  there  was  a  slight  amount  in 


UTILIZATION  OF  ALCOHOL. 


167 


the  second  wash-out,  so  that  it  is  not  certain  that  all  of  the  unabsorbed  al¬ 
cohol  was  completely  removed.  In  the  six  experiments  with  a  7.5  per  cent 
alcohol  solution,  there  was  only  one  experiment  in  which  a  second  wash  out 
showed  alcohol  in  the  material  obtained.  In  all  of  the  experiments  with  the 
10  per  cent  alcohol  solution  there  was  a  second  wash-out  which  was  without 
result  in  every  case,  showing  that  the  first  wash-out  removed  completely  the 
alcohol  which  was  unabsorbed,  that  is,  that  which  might  remain  in  the 
rectum  and  colon.  The  evidence  from  these  absorption  studies,  therefore, 
is  that  the  alcohol  when  injected  rectally  was  retained  by  the  body  and  entered 
into  its  tissues.  In  fact,  the  absorption  was  almost  complete,  being  usually 
over  98  per  cent. 

EXCRETION  OF  ALCOHOL  IN  URINE  AS  A  MEASURE  OF  UTILIZATION. 

In  this  research  there  were  two  groups  of  determinations  of  the  amount  of 
alcohol  excreted  in  the  urine,  one  series  in  which  the  alcohol  was  determined 
in  urine  collected  over  a  long  period  of  time,  and  a  second  series  in  which  the 
urine  was  collected  in  short  periods  of  time  and  the  alcohol  content  of  the 
individual  samples  determined.  In  all  but  two  experiments  in  which  alcohol 
was  given  by  rectum,  alcohol  was  found  in  the  urine.  This,  in  itself,  is  not  an 
indication  of  the  utilization  of  alcohol,  but  rather  evidence  to  the  contrary. 
It  is,  however,  evidence  of  the  fact  that  alcohol  has  entered  into  the  body  in 
such  a  way  that  it  is  eliminated  through  the  kidneys,  showing  that  the  alco¬ 
hol  has  traveled  from  the  point  of  entrance  and  been  distributed  throughout 
the  body.  One  might  take  the  ground  that  the  passage  of  alcohol  into  the 
urine  was  a  matter  of  simple  diffusion  from  the  rectum  directly  through  the 
bladder-wall  and  thus  into  the  urine.  Undoubtedly  there  is  direct  diffusion, 
as  animal  tissue,  even  if  not  active,  will  absorb  alcohol.  This  fact  has  been 
demonstrated  in  another  alcohol  study  1  in  which  the  effects  of  inhalation  of 
alcohol  by  fowl  and  its  distribution  throughout  the  body  was  observed.  In 
connection  with  these  observations,  dead  fowls  were  placed  in  an  atmosphere 
of  alcoholic  vapor  and  the  amount  of  alcohol  in  the  tissues  determined  after  a 
certain  period  of  time.  It  was  found  that  the  tissues  had  absorbed  an  appre¬ 
ciable  amount  of  alcohol,  thus  indicating  that  simple  diffusion  does  play  a 
certain  part  in  distribution  throughout  the  tissues  when  alcohol  is  introduced 
into  the  body.  To  assume  that  diffusion  was  the  sole  cause  for  the  elimina¬ 
tion  of  alcohol  in  the  urine  would  involve  the  assumption  that  no  alcohol 
reached  the  blood,  and  therefore  that  no  alcohol  was  eliminated  by  kidney  se¬ 
cretion.  This  assumption  is  highly  improbable,  as  on  two  or  three  occasions 
the  odor  of  alcohol  was  clearly  apparent  to  the  observer  in  the  breath  of  the 
subject,  and  there  were  subjective  impressions  such  as  sometimes  occur  after 
the  taking  of  alcohol,  i.  e.,  flushing  of  the  skin,  perspiration,  and  a  slight  sense 
of  intoxication.  (See  p.  165.) 

The  experiments  with  long  periods  of  collection  do  not  afford  any  particu¬ 
lar  evidence  as  to  the  rate  of  the  utilization  of  alcohol.  However,  they  do 
demonstrate  in  the  main  that  the  amount  of  alcohol  eliminated  is  greater 
when  the  concentration  of  alcohol  in  the  solution  injected  is  higher  and  when 
the  amount  injected  is  larger,  thus  indicating  that  a  larger  amount  of  alcohol 
is  absorbed  or  that  the  absorption  takes  place  so  rapidly  that  the  amount  in 
the  urine  reaches  a  higher  percentage. 


1  Carpenter  and  Babcock:  Am.  Journ.  Physiol.,  1919,  49,  p.  128. 


168 


HUMAN  METABOLISM  WITH  ENEMATA. 


The  striking  fact  about  the  matter  of  utilization  which  the  long  periods  of 
urine  collection  show  is  that  when  37.5  grams  of  alcohol  were  given  in  500  c.  c. 
of  a  7.5  per  cent  solution,  and  the  subject  slept  practically  the  entire  night, 
the  concentration  of  alcohol  in  the  urine  was  considerably  higher  (see  p.  43) 
than  in  all  the  other  cases.  While  the  amount  injected  was  somewhat  greater 
than  the  amount  usually  given  in  the  other  experiments,  nevertheless,  the 
concentration  was  so  high  in  these  night  experiments  that  it  leads  one  to 
think  that  sleep  may  have  had  an  influence  upon  the  utilization  of  alcohol 
and  that  there  may  not  be  so  complete  or  so  rapid  a  utilization  of  alcohol 
when  the  individual  is  asleep  immediately  after  or  during  the  taking  of  al¬ 
cohol  as  when  the  subject  is  active.  This  seems  the  more  probable,  as  the 
experiments  with  fowl  previously  referred  to  give  evidence  that  activity  dur¬ 
ing  the  time  of  inhalation  decreases  the  final  concentration  of  alcohol  in  the 
body.1  The  lower  alcohol  concentration  in  the  hens  which  were  most 
active  would  seem  to  point  to  the  probability  of  alcohol  serving  as  a  source 
of  energy  for  muscular  work. 

In  contrast  to  the  urine  studies  with  long  periods  of  collection,  the  experi¬ 
ments  in  which  the  urine  was  collected  in  short  periods  give  concrete  evidence 
of  the  utilization  of  alcohol  with  both  rectal  and  oral  administration.  The 
results  bring  out  clearly  the  fact  that  there  is  a  peak  in  the  concentration  of 
alcohol,  when  absorption  and  utilization  balance  one  another.  Within  the 
first  two  hours  after  the  alcohol  is  given,  its  absorption  is  faster  than  its 
utilization,  with,  in  consequence,  increasing  concentration  in  the  urine. 
One  must  not  conclude  that  this  rise  in  the  curve  indicates  the  amount  of 
absorption  and  from  the  concentrations  shown  attempt  to  compute  total 
absorption  values,  for  the  utilization  may  begin  immediately  after  ingestion; 
otherwise  the  peak  of  the  concentration  would  be  very  much  higher  than 
that  shown  in  most  of  the  experiments. 

It  is  of  interest  to  know  the  relationship  between  the  alcohol  in  the  urine 
and  that  in  the  body  and  between  the  changes  in  the  alcohol  contents  of  both 
urine  and  body.  Widmark,2  Nicloux,3  and  Chabanier  and  Loring4  made  a 
number  of  experiments  in  which  they  came  to  the  conclusion  that  the  alcohol 
in  the  urine  and  the  alcohol  in  the  blood  were  identical  at  any  given  point  of 
time.  Widmark  conducted  experiments  on  himself  in  which  he  took  alcohol, 
catheterized  himself,  then  collected  the  urine  in  very  short  periods,  and  also 
took  samples  of  blood  at  various  intervals.  He  found  that  the  amounts  of 
alcohol  in  the  urine  and  blood  were  almost  identical.  Chabanier  and  Loring 
carried  out  experiments  on  dogs  and  obtained  like  results.  They  both  came 
to  the  conclusion  that  the  distribution  of  alcohol  between  blood  and  urine 
was  a  matter  of  simple  diffusion,  and  therefore  that  blood  and  urine  were 
identical  in  concentration  of  alcohol. 

Miles,5  in  this  Laboratory,  has  studied  the  subject  in  great  detail,  using  a 
large  number  of  subjects,  collecting  the  urine  in  short  periods  (30  minutes 
each),  and  taking  blood  samples  at  intervals.  He  used  27.5  grams  of  alcohol 
in  water,  grape-juice,  and  alcohol-free  beer,  in  concentrations  of  2.75  and 

1  Carpenter  and  Babcock:  Am.  Journ.  Physiol.,  1919,  49,  p.  128. 

2  Widmark:  Skand.  Arch.  f.  Physiol.,  1916,  33,  p.  85. 

3  Nicloux:  Recherches  experimentales  sur  l’elimination  de  l’alcool  dans  l’organisme.  Deter¬ 

mination  d’un  “alcoolisme  congenital”.  Thesis,  Paris,  1900,  p.  7. 

4  Chabanier  and  Loring:  Compt.  rend.  Soc.  de  Biol.,  1916,  79,  p.  8. 

5 Miles:  Journ.  Pharm.  and  Exp.  Therapeutics,  1922,  20,  p.  265. 


UTILIZATION  OF  ALCOHOL. 


169 


27.5  per  cent.  In  practically  all  cases  he  found  that  in  the  first  45  minutes 
the  blood-alcohol  was  higher  than  that  in  the  urine,  but  at  the  end  of  the  first 
hour  the  alcohol  concentration  in  the  urine  was  invariably  higher  than  that 
in  the  blood,  in  many  cases  50  per  cent  higher.  The  blood  was  collected 
from  the  arm;  consequently  it  was  venous  blood,  and  Miles  calls  attention  to 
the  fact  that  the  difference  between  the  alcohol-contents  of  the  venous  and 
the  arterial  blood  might  be  sufficient  to  account  for  the  difference  between 
the  blood-alcohol  and  the  urine-alcohol. 

Grehant 1  points  out  that  the  concentration  of  alcohol  in  the  blood  after  a 
definite  quantity  has  been  taken  would  be  the  same  as  that  which  would  be 
expected  if  it  were  evenly  distributed  throughout  the  body.  For  example, 
when  a  dog  received  5  c.  c.  per  kilogram  of  body-weight,  the  alcohol  content 
of  the  blood  was  0.5  per  cent. 

Mellanby 2  found  with  a  dog  weighing  13.5  kg.  that  the  amount  of  alcohol 
in  the  blood  was  somewhat  higher  than  would  be  expected  according  to  Gre- 
hant’s  experiments,  and  says  that  the  Grehant  results  are  a  matter  of  coinci¬ 
dence.  He  believes  that  there  is  not  enough  basis  to  warrant  the  general 
assumption  made  by  Grehant.  Mellanby  brings  out  the  idea  that  the  con¬ 
centration  in  the  blood  of  the  dog  is  inversely  proportional  to  the  body- 
weight;  that  is,  a  dog  with  a  weight  of  11.75  kg.  had  a  concentration  of  92 
cubic  millimeters  per  100  grams  of  blood,  whereas  a  dog  weighing  13.5  kg. 
had  a  concentration  of  84  cubic  millimeters.  The  ratio  of  the  body-weights 
was  as  1 :  0.87,  while  the  inverse  ratio  of  the  alcohol  concentration  was  1 : 0.91. 

The  two  subjects  with  whom  most  of  the  experimental  work  here  reported 
was  done,  namely,  subject  A  and  subject  C,  weighed  54  kg.  and  69.7  kg., 
respectively.  If  25  grams  of  alcohol  were  distributed  throughout  the  body, 
there  would  be  an  average  concentration  of  0.46  mg.  per  gram  of  body-weight 
with  subject  A,  and  0.36  mg.  with  subject  C.  These  values  are  both  higher 
than  most  of  the  values  in  the  urine  obtained  with  these  subjects,  although 
subject  C,  on  May  6,  with  250  c.  c.  of  a  10  per  cent  alcohol  solution  had  a 
concentration  of  0.36  mg.  per  cubic  centimeter  of  urine,  which  is  about  the 
same  value  as  that  calculated  from  the  total  body-weight.  (See  table  12 
and  fig.  3,  pp.  46  and  51.) 

If,  however,  it  is  assumed  that  the  alcohol  is  distributed  throughout  the 
blood  only,  and  that  the  blood  is  one-twentieth  of  the  body-weight,  we  may 
use  as  the  basis  of  our  calculations  2.7  kg.  as  the  weight  of  A’s  blood  and  3.5 
kg.  as  the  weight  of  C’s  blood.  With  25  grams  of  alcohol  distributed  through 
the  blood,  the  concentration  would  be  9.3  mg.  per  gram  of  blood  for  A  and  7.1 
mg.  per  gram  of  blood  for  C. 

If  we  assume  that  60  per  cent  of  the  body  is  water,  we  may  make  similar 
calculations  of  the  distribution  of  alcohol  throughout  the  water  in  the  bodies 
of  these  subjects.  The  water  contained  in  A’s  body  would  weigh  32.4  kg., 
and  in  C’s  41.8  kg.  With  25  grams  of  alcohol,  the  concentration  with  sub¬ 
ject  A  would  be  0.77  mg.  per  gram  of  water  and  with  C,  0.60  mg.  per  gram  of 
water. 

These  calculations  of  concentration  of  alcohol  in  the  body  all  give  higher 
values  than  the  highest  found  in  the  analysis  of  urine.  Miles  has  shown  that 
the  urine-alcohol  was  higher  than  that  in  the  venous  blood,  so  that  probably 

*  Grehant:  Compt.  rend.  Soc.  de  Biol.,  1881,  1896,  1899. 

*  Mellanby:  Med.  Research  Com.,  Sp.  Rept.  Ser.  No.  31,  1919. 


170 


HUMAN  METABOLISM  WITH  ENEMATA. 


there  is  no  tissue  whose  alcohol  concentration  is  higher  than  the  alcohol  in 
either  blood  or  urine.  The  fact  that  at  the  end  of  2  hours  the  urine  rarely,  if 
ever,  had  an  alcohol  concentration  even  approximating  any  of  the  calculated 
concentrations  in  the  preceding  paragraphs  is  of  significance,  because  it 
points  towards  a  rapid  utilization  of  alcohol  in  the  first  2  hours.  The  objec¬ 
tion  to  this  idea  would  be  that  possibly  not  all  of  the  alcohol  had  been 
absorbed. 

Unfortunately,  there  are  very  few  experiments  in  the  series  here  reported 
which  give  an  idea  as  to  the  actual  rapidity  with  which  alcohol  is  absorbed. 
Most  of  the  absorption  experiments  indicate  nearly  complete  absorption; 
consequently,  whether  the  absorption  required  all  the  time  the  enema  was 
retained  or  whether  it  took  less  time  can  not  be  determined  from  the  data. 
On  December  20  there  was  an  experiment  with  subject  C  (see  table  2,  p.  27) 
in  which  25  grams  of  alcohol  were  given  in  a  5  per  cent  solution  and  retained 
only  2  hours  and  3  minutes.  The  analysis  of  the  material  from  the  wash-out 
indicated  an  absorption  of  80  per  cent.  In  an  experiment  with  the  same  sub¬ 
ject  on  November  29,  21  grams  were  retained  2  hours  and  45  minutes,  with  an 
absorption  of  98  per  cent.  With  a  7.5  per  cent  solution  there  were  two  ex¬ 
periments  in  which  the  time  of  retention  was  short.  (See  table  3,  p.  29.) 
On  April  10  there  was  an  absorption  of  98  per  cent  of  350  c.  c.  (26.25  grams  of 
alcohol)  when  the  enema  was  retained  1  hour,  and  on  April  15  there  was  an 
absorption  of  87  per  cent  of  500  c.  c.  (37.5  grams  of  alcohol)  in  1  hour  and  4 
minutes.  With  a  10  per  cent  alcohol  solution  there  was  an  experiment  with 
subject  A  on  March  24  (see  table  4,  p.  30)  in  which  the  absorption  was  100 
per  cent,  with  a  retention  for  2  hours  and  30  minutes  of  260  c.  c.  (26  grams). 
While  these  results  are  variable,  they  all  show  that  the  absorption  of  5,  7.5, 
and  10  per  cent  solutions  of  alcohol  given  by  rectum  is  very  rapid.  As  the 
minimum  absorption  was  80  per  cent  in  2  hours,  it  must  be  concluded  that 
the  cause  for  the  difference  between  the  concentration  of  alcohol  in  urine  as 
found  and  the  theoretical  calculated  values  shown  in  the  preceding  para¬ 
graphs  is  not  due  to  the  slowness  of  absorption.  If  these  low  urine-alcohol 
values  are  not  due  to  lack  of  absorption  of  the  alcohol  from  the  rectal 
tract,  then  they  must  be  due  to  rapid  utilization  in  the  first  2  hours. 

As  pointed  out  previously,  the  concentration  of  alcohol  in  the  body  at  any 
given  moment  is  a  resultant  of  the  balance  between  the  absorption  and  utili¬ 
zation.  The  first  collection  of  urine  in  most  of  our  experiments  showed  the 
highest  values  of  the  series  for  alcohol  concentration.  In  other  words,  this 
collection  probably  was  not  taken  at  such  a  time  that  the  absorption  was 
faster  than  the  utilization.  (See  pp.  52  and  168.)  Also,  the  majority  of  the 
first  collections  were  within  the  first  2  hours.  Consequently,  if  we  can  cal¬ 
culate  the  total  amount  of  alcohol  present  in  the  body  at  the  first  urine 
collection  and  assume  that  the  difference  between  this  amount  and  the 
amount  injected  represents  the  amount  utilized,  we  can  gain  information  as 
to  the  theoretical  rate  of  utilization  of  alcohol.  Also,  calculating  the  total 
amount  present  at  the  subsequent  collections  will  give  information  as  to  the 
theoretical  rate  of  utilization  throughout  the  remainder  of  the  experiment. 
The  problem,  then,  is  to  find  the  relationship  between  the  concentration  of 
alcohol  in  the  body  and  that  in  the  urine. 

In  the  study  upon  fowls  previously  mentioned,  the  alcohol  concentration 
in  the  tissues  and  in  the  blood  was  determined  at  various  times,  and  it  is 


UTILIZATION  OF  ALCOHOL. 


171 


possible  to  make  a  comparison  between  the  concentration  of  the  alcohol  in 
the  blood  and  that  in  the  whole  body.  While  there  are  variations  in  this 
relationship,  it  is  of  sufficient  constancy  so  that  it  may  be  said  that  the 
concentration  of  alcohol  averages  throughout  the  body  about  two-thirds  the 
concentration  in  the  blood.  Consequently,  when  we  know  the  concentration 
of  alcohol  in  the  blood  of  fowls,  we  may  then  compute  the  average  concentra¬ 
tion  of  alcohol  throughout  their  bodies. 

To  apply  this  relationship  for  fowl  to  the  human  body  requires  an  assump¬ 
tion,  for  such  a  relationship  has  not  been  determined  for  humans.  A  com¬ 
parison  of  the  composition  of  the  fowl's  body  with  that  of  the  human  body 
will,  however,  give  some  suggestion  as  to  whether  such  application  may  be 
made.  The  composition  of  the  whole  human  body  as  given  by  Yierordt 1  is 
water  67.6  per  cent,  protein  bodies  and  derivatives  20.1  per  cent,  fat  2.5  per 
cent,  and  salts  9.2  per  cent.  Bouchard  2  gives  different  figures,  these  being 
water  66  per  cent,  protein  16  per  cent,  fat  13  per  cent,  and  ash  5  per 
cent.  The  average  composition  of  fowls  as  purchased  3  is  reported  as  water 
47  per  cent,  protein  14  per  cent,  fat  12  per  cent,  and  ash  less  than  1  per  cent. 
The  extreme  variation  for  both  water  and  fat  contents  is  given  as  15  per  cent. 
The  hen  is  therefore  drier  than  man  and,  according  to  Vierordt's  figures,  is 
also  fatter.  Both  of  these  differences  would  tend  to  widen  the  ratio  between 
the  concentration  in  the  whole  body  and  that  of  the  blood,  as  it  was  found  4 
that  fat  absorbed  the  smallest  amount  of  alcohol  and,  in  general,  the  greater 
the  water-content  of  the  tissue,  the  higher  was  the  concentration  of  alcohol. 
On  the  contrary,  the  salts  in  man's  body  are  larger  in  amount  than  the  ash  in 
the  body  of  the  fowl,  and  while  these  are  not  strictly  comparable,  the  differ¬ 
ence  is  of  significance. 

According  to  this  comparison  of  body  composition,  therefore,  the  ratio 
found  with  hens  for  the  relationship  between  the  concentration  of  alcohol  in 
the  blood  and  its  concentration  in  the  whole  body,  if  used  for  humans,  will 
assume  a  larger  difference  between  the  two  than  is  actually  the  case.  How¬ 
ever,  notwithstanding  the  fact  that  with  humans  the  concentrations  of 
alcohol  in  the  blood  and  in  the  whole  body  would  be  more  nearly  similar 
than  with  fowl,  we  may,  for  purposes  of  discussion,  consider  that  the  con¬ 
centration  of  alcohol  in  the  body  is  two-thirds  that  in  the  blood. 

The  results  obtained  by  Miles  in  his  determinations  of  the  alcohol  in  the 
urine  and  blood  of  his  subjects  make  the  use  of  the  urine-alcohol  as  a  basis  for 
calculating  the  rate  of  disappearance  of  alcohol  from  the  body  in  the  present 
research  somewhat  complicated.  One  must,  in  consequence  of  his  results, 
assume  that  at  the  end  of  the  first  hour  the  concentration  of  alcohol  in  the 
blood  is  at  least  two-thirds  that  in  the  urine.  It  should  be  noted,  however, 
that  the  urine  and  blood  curves  given  by  Miles  tend  to  approach  one  another 
in  the  second  hour,  and  their  relationship  in  the  third  and  fourth  hours,  over 
which  many  of  our  experiments  were  extended,  can  not  be  ascertained  at 
this  time.  The  results  of  the  present  research  have  established  the  fact  that 

1  Vierordt:  Daten  u.  Tabellen  f.  Mediziner.  Jena,  1906,  3d  Aufl.,  p.  378. 

2  Bouchard:  Compt.  rend.,  1897,  124,  p.  844. 

5  Atwater  and  Bryant:  U.  S.  Dept.  Agr.,  Office  Exp.  Sta.  Bull.  No.  28,  1906,  p.  44.  It  would  seem 
as  though  this  analysis  must  represent  only  the  flesh  portion  of  the  fowl  and  not  include  the 
skeleton,  because  of  the  low  amount  of  ash.  If  both  groups  of  data  for  men  and  fowl  were 
calculated  on  an  ash-free  basis,  the  argument  would  be  in  no  way  altered. 

4  Carpenter  and  Babcock:  Am.  Journ.  Physiol.,  1919,  49,  p.  128. 


172 


HUMAN  METABOLISM  WITH  ENEMATA. 


25  grams  of  alcohol  will  disappear  from  the  urine  in  5  to  6  hours  (see  p.  55)  and 
presumably  during  this  time  it  must  also  have  disappeared  from  the  blood. 

Rosemann  1  takes  exception  to  the  idea  that  the  disappearance  of  the 
alcohol  from  the  urine  is  an  indication  of  the  fact  that  the  alcohol  is  no  longer 
present  in  the  blood.  While  the  experimental  results  available  at  the  time 
of  Rosemann’s  statement,  as  well  as  the  technique  then  used,  might  warrant 
such  a  criticism,  at  the  present  time  the  methods  for  the  determination  of 
alcohol  are  so  exact  that  when  no  alcohol  is  found  in  the  urine  it  can  hardly 
be  assumed  that  there  is  an  appreciable  amount  of  alcohol  in  the  blood. 
This  is  borne  out  by  the  fact  that  the  results  obtained  in  experiments  with 
fowl  previously  referred  to  indicate  that,  except  in  the  egg,  there  is  no  large 
store  of  alcohol  in  any  tissue  which  is  materially  higher  than  that  in  the 
blood,  even  though  Lenoble  and  Daniel 2  maintain  that  the  cerebrospinal 
fluid  retains  alcohol  several  days  after  it  has  disappeared  from  the  blood. 

For  the  purpose  of  calculating  the  rate  of  utilization  of  alcohol,  we  may 
assume  that  the  concentration  of  alcohol  in  the  blood  is  the  same  as  that  in 
the  urine,  and  that  the  relationship  between  the  concentration  of  alcohol  in 
the  blood  and  that  in  the  whole  body  is  as  1  to  0.67.  (See  p.  171.)  To 
illustrate  the  calculation  of  the  rate  of  utilization  by  this  method,  use 
may  be  made  of  the  data  obtained  in  an  experiment  in  which  there 
was  a  complete  disappearance  of  alcohol  from  the  urine,  namely,  that 
with  subject  A  on  December  15,  1915.  (See  table  12,  p.  46.)  To  find 
the  theoretical  amount  of  alcohol  present  in  the  body  for  each  urine 
period,  the  concentration  of  alcohol  in  the  urine  obtained  from  each 
collection  is  multiplied  by  0.67  and  the  body-weight  of  the  subject  (54 
kg.).  As  the  urine  collected  was  the  amount  secreted  throughout  the  whole 
period  and  not  that  at  any  one  moment,  we  must  also  assume  that  the  urine 
value  obtained  represents  the  average  concentration  of  alcohol  for  this 
length  of  time,  i.  e.,  the  amount  of  alcohol  present  at  the  middle  of  the  period. 
The  calculations  of  the  theoretical  amounts  present  in  the  body  for  the  suc¬ 
cessive  urine  periods  are  given  in  table  29.  They  show  that  for  the  period 
ending  at  6h  30m  p.  m.  (1  hour  and  12  minutes  after  the  injection  began),  the 
alcohol  in  the  whole  body  averaged  9.8  grams,  and  for  the  period  ending  at 
7  p.  m.  (1  hour  and  42  minutes  after  the  beginning  of  the  injection),  it  aver¬ 
aged  11.6  grams,  that  is,  the  alcohol  in  this  period  was  absorbed  more  rapidly 
than  it  was  utilized.  Deducting  the  latter  amount  from  the  total  amount 
actually  injected  (21.5  grams)  leaves  9.9  grams  of  alcohol  apparently  utilized 
in  1  hour  and  27  minutes,  i.  e.,  from  the  beginning  of  the  injection  to  the 
middle  of  the  second  period.  This,  if  true,  would  be  an  extraordinarily 
rapid  utilization.  For  the  period  ending  at  7h  28m  p.  m.  (2  hours  and  10 
minutes  after  the  injection  began),  the  amount  present  was  9.8  grams  and  the 
total  utilization  up  to  this  time  11.7  grams  as  compared  with  9.9  grams  for 
the  preceding  period.  Thus,  the  additional  utilization  in  approximately  30 
minutes  was  but  1.8  grams,  indicating  a  rapid  fall  in  rate  of  utilization.  The 
utilization  in  the  next  four  periods  would  then  be  2.5,  2.9,  2.8,  and  0.3  grams, 
respectively.  At  the  end  of  the  fifth  hour  the  alcohol  had  disappeared. 

We  may  calculate,  also,  the  rate  per  minute  at  which  the  alcohol  disap- 

1  Rosemann:  Oppenheimer’s  Handbuch  der  Biochemie  des  Menschen  und  der  Thiere.  Jena,  1911, 
4,  p.  422. 

*  Lenoble  and  Daniel:  Bull,  de  l’Acad.  de  Med.,  1919,  82,  p.  160. 


UTILIZATION  OF  ALCOHOL. 


173 


peared  from  the  beginning  of  the  injection  to  the  middle  of  each  period.  The 
first  period  need  not  be  considered,  as  during  this  time  the  alcohol  was  being 
absorbed  and  the  urine  collected  included  a  certain  amount  which  had  been 
secreted  before  the  injection  began.  For  the  period  ending  at  7  p.  m.,  we  use 
87  minutes  as  the  basis  of  calculation  to  the  middle  of  the  period,  and  have 
0.11  gram  as  the  amount  utilized  per  minute.  As  the  duration  of  each 
successive  period  is  added,  the  rate  per  minute  gradually  decreases  until 
for  the  whole  time  the  rate  of  utilization  averages  0.075  gram  per  minute. 
This  indicates  a  change  in  rate  as  the  observations  continued. 

Table  29. — Calculation  of  rate  of  disappearance  from  the  body  and  theoretical  utilization  of 

alcohol. 


End  of  period. 

Calculation  of  average  alcohol 
present  in  the  body 
during  period. 

(w  X  a  X  b)a 

Alcohol  theo¬ 
retically 
utilized,  as 
shown  by 
difference  be¬ 
tween  amount 
injected  (21.5 
gm.)  and 
amount  pres¬ 
ent  in  body. 

Utilization  per 
minute,  calcu¬ 
lated  to  middle 
of  period  from 
time  injection 
began.6 

Calculation 
of  utiliza¬ 
tion  per 
minute  in 
each 
period. 

Time. 

Amount. 

grams. 

grams. 

min. 

gram. 

gram. 

6h  30m  p.  m. 

0.27  X  0.67  X  54=  9.78 

[11.72] 

c36 

0.33  > 

d0.110 

7  00 

.32  X  .67  X  54  =  11.57 

9.93 

87 

.11  < 

l 

.062 

7  28 

.27  X  .67  X  54=  9.78 

11.72 

116 

.10  ^ 

.077 

8  05 

.20  X  .67  X  54=  7.24 

14.26 

149 

.096  j 

.071 

8  51 

.12  X  .67  X  54=  4.34 

17.16 

190 

.090  l 

.064 

9  33 

.042  X  -67  X  54=  1.52 

19.98 

234 

.085  <j 

.009 

10  03 

.033  X  .67  X  54=  1.19 

20.31 

270 

.075  <j 

.079 

.  0.00 

21.50 

e285 

.075  J 

°  w  =  concentration  of  alcohol  in  the  urine  (mg.  per  c.  c.)  in  experiment  with  A  on  December  15. 
a  =  relationship  between  the  concentration  of  alcohol  in  the  blood  and  that  in  the  body,  the 
assumption  being  made  that  the  concentration  of  alcohol  is  the  same  in  the  blood  as  in  the 
urine.  5  =  body- weight  of  subject  A  (kg.). 

6  The  injection  was  given  between  5h  18m  and  5h  47m  p.  m. 
e  To  middle  of  interval  between  beginning  of  injection  and  end  of  first  period. 
d  Assumed  from  utilization  per  minute  to  middle  of  second  period. 
e  Includes  15  minutes,  the  remainder  of  the  seventh  period. 


The  rate  of  utilization  per  minute  for  the  individual  periods  may  also  be 
calculated,  basing  this  calculation,  also,  upon  the  lapse  of  time  from  the  mid¬ 
dle  of  one  period  to  the  middle  of  the  succeeding  period.  We  find  the  utiliza¬ 
tion  rate  by  this  method  of  statement  to  be  greatest  at  the  beginning  of  the 
observations  (0.11  gram  per  minute)  and  least  for  the  period  between 
9h  33m  p.  m.  and  10h  03m  p.  m.  Whatever  way  the  calculation  is  made, 
the  indications  are  that  the  rate  of  utilization  is  greatest  during  the  first  2\ 
hours.  To  disprove  this  it  would  be  necessary  to  make  one  of  three  changes 
in  the  method  of  calculation:  (1)  raise  the  amount  present  in  the  body,  i.  e., 
the  amount  unutilized,  for  the  periods  ending  at  6h  30m  p.  m.,  7  p.  m., 


174 


HUMAN  METABOLISM  WITH  ENEMATA. 


and  7h  28m  p.  m.;  (2)  assume  that  absorption  had  been  incomplete  and  it 
was  still  progressing  after  7h  28m  p.  m. ;  or  (3)  assume  that  there  was  some 
tissue  in  the  body  whose  alcohol-content  was  much  higher  than  that  of  the 
urine,  this  being  still  in  question.  We  have  evidence  that  the  absorption  is 
not  complete  at  the  end  of  the  first  period  (at  6h  30m  p.  m.),  as  the  con¬ 
centration  was  higher  in  the  urine  in  the  period  ending  at  7  p.  m.  Further¬ 
more,  the  fall  in  concentration  in  the  period  ending  at  7h  28m  p.  m.  was  not 
so  great  as  in  the  two  succeeding  periods,  so  that  the  absorption  as  indicated 
by  the  concentration  of  alcohol  in  the  urine  was  probably  not  complete 
until  between  7h  28m  and  8h  05m  p.  m.  This  was  about  2|  hours  after  the 
injection  began,  and  it  corresponds  very  closely  to  the  probable  time  of 
complete  absorption  as  shown  in  the  absorption  experiments.  (See  p.  27.) 

The  amount  of  alcohol  calculated  to  be  present  in  the  body  could  be  raised 
by  assuming  a  narrower  ratio  than  1  to  0.67  between  the  concentration  in  the 
urine  and  that  in  the  whole  body.  There  is  some  warrant  for  this,  as  the 
percentage  of  water  in  the  human  body  is  larger  than  that  in  the  hen’s  body. 
However,  if  the  alcohol  content  is  calculated  from  the  water-content  of  the 
body,  the  concentration  would  be  multiplied  by  0.60  of  the  body- weight, 
instead  of  by  the  factor  0.67,  which  would  tend  to  lower  all  the  values  and 
indicate  an  even  greater  utilization  of  alcohol  in  the  first  2  or  3  hours. 

This  discussion  is  based  upon  certain  assumptions  which  admittedly  are 
difficult  to  prove.  If  we  begin  with  the  assumption  that  the  concentration 
of  alcohol  in  the  blood  is  two-thirds  as  high  as  the  concentration  in  the  urine, 
it  would  be  necessary  to  lower  materially  the  figures  in  the  first  hour  or  two 
of  the  observations.  The  majority  of  Miles’s  experiments  were  not  extended 
beyond  2  hours  after  the  solution  was  taken,  and  nearly  all  of  the  experiments 
indicate  at  the  end  of  that  time  a  tendency  for  the  concentrations  in  blood  and 
urine  to  approach  each  other,  and  also  for  the  higher  concentrations  to  be 
nearer  together.  If  we  assume  for  the  first  three  periods  a  difference  between 
the  concentrations  of  alcohol  in  the  blood  and  urine,  the  alcohol  utilized  in  the 
first  2  hours  would  be  much  greater  than  that  shown  in  table  29.  The  utilization 
would  also  be  greatest  when  the  greatest  fall  occurred,  which  seems  reasonable 
according  to  the  curves  obtained.  In  fact,  the  question  may  be  raised  as  to 
whether  the  rate  of  utilization  of  alcohol  does  not  follow  more  or  less  the  mass 
law,  that  is,  the  rate  is  proportional  to  the  amount  present.  This  would  indi¬ 
cate  a  rapid  utilization  at  first,  with  a  gradually  declining  rate  of  utilization. 
Some  of  the  curves  indicate  this  change  in  rate,  while  others  show  a  fall  too 
steady  to  be  a  mass-law  effect. 

One  fact  must  be  accepted,  namely,  that  in  about  5  hours  the  21.5  grams  of 
alcohol  are  actually  utilized,  and  this  gives  an  average  rate  of  0.075  gram  per 
minute  or  4.5  grams  per  hour.  At  the  end  of  that  time  no  alcohol  was  found 
in  the  urine.  By  present  methods,  it  is  possible  to  detect  1  mg.  of  alcohol 
in  100  c.  c.  of  urine;  consequently,  if  no  alcohol  appeared  in  the  urine,  the  al¬ 
cohol  present  in  the  body  must  be  so  small  that  it  can  not  be  detected. 

The  exact  peak  or  highest  point  in  the  curve  for  alcohol  in  urine  can  not  be 
obtained  either  for  the  time  or  the  concentration,  but  it  must  be  within  the 
first  2  hours,  and  the  concentration  is  not  materially  higher  at  any  time  than 
the  highest  point  observed.  While  the  urine  may  not  have  the  same  alcohol 
concentration  as  the  blood,  its  concentration  must  be  dependent  upon  the 
concentration  in  the  blood,  as  it  is  independent  of  diuresis  or  the  amount  of 


UTILIZATION  OF  ALCOHOL. 


175 


urine  which  is  voided.  If  this  is  so,  the  concentration  must  be  determined  by 
the  concentration  of  the  liquid  which  is  secreted  by  the  kidneys,  and  this  in 
turn  by  the  concentration  of  the  blood  flowing  through  the  kidneys.  There 
is  thus  a  definite  relationship  between  the  concentration  of  alcohol  in  the 
blood  and  its  concentration  in  the  urine. 

The  results  of  the  studies  of  the  alcohol  in  urine  in  short  periods  indicate 
that  the  utilization  of  alcohol  in  the  first  1  \  hours  must  be  extremely  high,  be¬ 
cause  any  method  of  calculation  which  may  be  used  shows  that  the  amount  of 
alcohol  left  in  the  body  at  the  end  of  If  to  2  hours  is  not  large,  and  the  utiliza¬ 
tion  of  alcohol  is  practically  complete  at  the  end  of  5  hours.  This  would 
mean  that  with  25  grams  of  alcohol  there  was  a  utilization  on  the  average  of 
5  grams  of  alcohol  per  hour.  The  mathematical  effect  of  this  upon  the 
respiratory  exchange  will  be  considered  later. 

It  may  seem  that  this  discussion  is  of  little  value,  because  we  are  not  able 
to  arrive  at  any  definite  method  of  calculating  the  utilization  of  alcohol. 
These  theoretical  calculations  do  point  out,  however,  the  great  utility  of 
studies  of  absorption  and  of  the  concentration  in  the  urine  and  blood  when 
carried  on  simultaneously.  A  given  quantity  may  be  introduced  rectally 
and  the  unabsorbed  portion  determined,  at  the  end  of  half-hour  periods,  for 
example.  This  would  provide  information  as  to  the  amount  available  in  the 
body,  and  by  following  the  urinary  concentration  of  alcohol  the  time  of  disap¬ 
pearance  can  be  determined.  By  varying  the  quantity  injected  and  the  time 
of  retention,  a  large  amount  of  information  may  be  obtained  regarding  the 
disappearance  of  alcohol  from  the  body.  If,  in  addition,  studies  are  made 
with  the  use  of  a  stomach-tube,  an  opportunity  is  given  for  comparing  the 
utilization  according  to  the  method  of  introduction. 

UTILIZATION  OF  ALCOHOL  IN  RECTAL  FEEDING  AS  INDICATED  BY  THE 

RESPIRATORY  EXCHANGE. 

The  original  plan  of  these  investigations  was  to  determine  the  respiratory 
exchange  after  the  rectal  injection  of  alcohol  with  the  idea  of  finding  whether 
or  not  the  alcohol  was  utilized  and  of  employing  the  change  in  the  respiratory 
quotient  as  an  index  of  such  utilization. 

Under  ordinary  conditions  of  nutrition,  the  various  functions  of  the  human 
organism  are  accompanied  by  the  metabolism  of  three  groups  of  substances — 
protein,  fat,  and  carbohydrate.  The  fats  and  carbohydrates  are  considered 
to  be  metabolized  completely  to  carbon  dioxide  and  water,  while  a  portion  of 
the  protein  escapes  oxidation  and  passes  into  the  urine.  The  composition 
of  carbohydrate  is  such  that  in  its  metabolism  the  ratio  of  the  volume  of 
carbon  dioxide  formed  to  that  of  the  oxygen  used  is  1.00.  The  fats  contain 
so  small  an  amount  of  oxygen  that  the  ratio  is  less,  namely,  0.70.  With 
protein  the  ratio  for  the  part  actually  burned  is  0.81.  These  ratios  are  the 
well-known  respiratory  quotients.  The  nitrogen  in  the  urine  eliminated  in  a 
given  period  of  time  is  considered  to  be  a  measure  of  the  protein  katabolized. 
Since  the  carbon  dioxide  and  oxygen  involved  in  the  metabolism  of  1  gram  of 
protein  is  known,  the  amount  of  carbon  dioxide  given  off  and  oxygen  absorbed 
in  the  katabolism  of  carbohydrate  and  fat  may  be  calculated  by  subtracting 
the  amount  due  to  the  protein  metabolized  from  the  total  values  obtained  for 
carbon  dioxide  and  oxygen.  The  apportionment  of  the  katabolism  between 
carbohydrate  and  fat  may  then  be  made  by  utilizing  the  quantities  of  carbon 


176 


HUMAN  METABOLISM  WITH  ENEMATA. 


dioxide  produced  and  oxygen  absorbed  when  carbohydrate  and  fat  are 
metabolized.  By  means  of  simultaneous  equations,  the  oxygen  and  carbon 
dioxide  may  be  apportioned  between  these  two,  or  one  may  utilize  the  tables 
of  Zuntz  and  Schumburg  as  extended  by  Williams,  Riche,  and  Lusk.1  The 
apportionment  of  the  metabolism  among  these  three  substances  presents, 
therefore,  no  serious  complications. 

When,  however,  a  fourth  substance,  such  as  alcohol,  enters  into  the 
metabolism  to  a  significant  extent,  the  problem  is  very  much  more  com¬ 
plicated.  The  chief  question  is  which  one  or  more  of  the  three  groups  of 
substances  (protein,  fat,  or  carbohydrate)  does  alcohol  replace?  Further¬ 
more,  what  effect  does  the  replacement  have  on  the  respiratory  quotient  and 
on  the  relation  of  oxygen  absorption  and  carbon-dioxide  production  to  heat 
production? 

Rosemann  2  assumed  that  alcohol,  when  metabolized,  replaces  all  three 
substances  in  the  metabolism  in  the  proportions  in  which  they  occurred  be¬ 
fore  the  alcohol  was  ingested;  that  is  to  say,  if  50  per  cent  of  the  total 
metabolism  was  replaced  by  alcohol,  then  the  previous  metabolism  of  pro¬ 
tein,  fat,  and  carbohydrate  would  each  be  reduced  50  per  cent.  For  cal¬ 
culating  the  amount  of  oxygen  involved  in  the  metabolism  of  alcohol,  he 

gives  the  formula  Oa  =  0~ — 

In  this  formula  Oa  represents  the  oxygen  used  in  burning  alcohol,  0  the 
total  oxygen  utilized,  q  the  respiratory  quotient  before  alcohol  was  given,  qa 
the  quotient  after  the  ingestion,  and  0.67  the  respiratory  quotient  for  alcohol. 
This  calculation  involves  the  assumption  that  the  oxygen  utilized  is  the  same 
before  and  after  the  taking  of  alcohol. 

Rosemann  has  calculated  the  amount  of  oxygen  used  in  the  metabolism 
of  alcohol  for  some  of  the  experiments  of  Geppert.3  Large  quantities  of 
alcohol  were  taken  in  these  experiments  (from  70  to  125  c.  c.)  and  the 
respiratory  quotient  before  the  taking  of  alcohol  varied  from  0.83  to  0.90. 
The  respiratory  quotient  after  the  ingestion  of  alcohol  varied  from  0.72  to 
0.79.  The  values  obtained  by  Rosemann  with  his  formula  for  calculating 
the  oxygen  used  for  alcohol  combustion  varied  from  44  to  77  per  cent  of  the 
total,  indicating  that  the  proportion  of  the  metabolism  due  to  the  alcohol  was 
considerable.  The  amount  of  alcohol  burned  according  to  this  calculation 
varied  from  4.2  grams  to  9.6  grams  per  hour,  the  lower  figure  being  somewhat 
like  the  value  which  has  been  estimated  for  the  experiments  here  reported 
when  the  alcohol  in  the  urine  was  considered. 

Higgins  4  used  the  formula  of  Rosemann  for  calculating  the  amount  of 
alcohol  utilized  in  experiments  on  man,  and  came  to  the  conclusion  that  the 
fall  in  the  respiratory  quotients  and  the  calculated  amounts  of  alcohol  con¬ 
sumed  are  not  markedly  different  for  45  and  30  c.  c.  of  alcohol.  He  calcu¬ 
lated  that  on  the  average  about  27  per  cent  of  the  total  oxygen  was  consumed 
in  burning  the  alcohol  with  both  30  c.  c.  and  45  c.  c.,  the  variation  being  from 
7  to  54  per  cent.  The  average  amount  of  alcohol  burned  per  hour  was  calcu¬ 
lated  as  3.46  c.  c.  He  states  that  it  would  take  approximately  8  hours  for  the 


1  Williams,  Riche,  and  Lusk:  Journ.  Biol.  Chem.,  1912,  12,  p.  357. 

2  Rosemann:  Oppenheimer’s  Handbuch  d.  Biochem.,  1911,  4,  (1),  p.  423. 

3  Geppert:  Arch.  f.  exp.  Path.  u.  Pharmakol.,  1887,  22,  p.  367. 

4  Higgins:  Journ.  Pharm.  and  Exp.  Therapeutics,  1917,  9,  p.  467. 


UTILIZATION  OF  ALCOHOL. 


177 


total  consumption  of  30  c.  c.  and  as  much  as  12  hours  for  45  c.  c.  of  alcohol, 
Higgins  likewise  gives  a  table  showing  that  the  greater  the  initial  respiratory 
quotient  is  when  alcohol  is  ingested,  the  greater  will  be  both  the  fall  due  to 
the  taking  of  the  alcohol  and  the  percentage  of  the  total  oxygen  which  is  used 
for  alcohol  metabolism. 

Durig  and  coworkers  studied  the  carbohydrate-sparing  action  of  alcohol,1 
using  the  Zuntz-Geppert  apparatus  for  determining  the  respiratory  exchange. 
In  some  experiments  they  gave  100  grams  of  dextrose  and  100  grams  of  levu- 
lose  and  followed  the  respiratory  exchange  from  period  to  period  for  4  hours. 
With  dextrose  alone  there  was  a  slow  but  marked  rise  in  the  respiratory  quo¬ 
tient,  with  a  change  in  some  cases  from  approximately  0.85  to  over  1.00. 
When,  however,  alcohol  was  given  with  the  dextrose,  or  1  hour  and  40  minutes 
afterwards,  the  rise  in  the  quotient  found  with  dextrose  alone  did  not  take 
place,  or  the  upward  movement  stopped  when  the  alcohol  was  given.  The 
same  general  effect  was  found  when  alcohol  was  given  in  the  levulose  experi¬ 
ments.  In  one  experiment  portions  containing  30  grams  of  levulose  each 
were  given  at  intervals;  in  another  experiment  the  same  procedure  was  fol¬ 
lowed,  but  30  c.  c.  of  alcohol  were  given  about  40  minutes  after  the  first  por¬ 
tion  of  sugar  had  been  ingested.  In  the  experiment  with  levulose  alone,  the 
respiratory  quotient  remained  at  or  near  1.00,  but  with  levulose  and  alcohol 
there  was  an  immediate  fall  in  the  quotient  as  soon  as  the  alcohol  was  given, 
which  continued  until  the  quotient  was  even  lower  than  before  the  levulose 
was  ingested.  Assuming  that  the  alcohol  replaced  carbohydrate,  the  authors 
calculated  70  mg.  of  alcohol  were  burned  per  minute,  or  4.2  grams  of  alcohol  in 
1  hour,  and  that  in  the  first  4  hours,  16.8  grams  were  utilized  of  the  24  grams 
given.  The  experiments  show  very  clearly  that  the  giving  of  alcohol  with 
carbohydrate,  or  after  the  rise  in  respiratory  quotient  has  begun,  either 
lowers  the  quotient  or  prevents  the  rise  which  would  normally  take  place  due 
to  the  ingestion  of  carbohydrate.  Whether  this  rise  in  quotient  is  due  to 
a  combustion  of  carbohydrate  or  a  change  of  carbohydrate  to  fat,  the  inter¬ 
ruption  is  complete,  so  that  the  introduction  of  alcohol  into  the  organism 
changes  a  condition  of  metabolism  in  which  carbohydrate  is  the  predom¬ 
inating  factor. 

In  order  to  obtain  an  idea  as  to  the  theoretical  effect  of  the  utilization  of 
alcohol  and  its  replacement  of  other  materials  in  ordinary  metabolism,  a  table 
has  been  prepared  giving  the  results  of  calculations  in  which,  with  varying 
apportionments  of  protein,  fat,  and  carbohydrate  in  the  initial  metabolism, 
alcohol  has  been  made  to  replace  a  certain  mathematical  proportion  of  the 
energy  production  (1  per  cent)  of  one  or  more  of  the  other  three  substances. 
(See  table  32.)  These  calculations  show  the  effect  of  such  replacement  upon 
the  respiratory  quotient.  The  values  utilized  in  this  calculation  are  those 
for  glycogen,  human  fat,  human  protein,  and  ethyl  alcohol.2  (See  table  30.) 

The  method  of  calculating  the  respiratory  quotient  and  also  the  calorific 
equivalents  of  oxygen  and  carbon  dioxide  is  illustrated  in  table  31.  In  this 
sample  calculation  it  has  been  assumed  that  the  total  metabolism  was  2,000 
calories,  the  substances  metabolized  being  in  the  following  proportions :  pro¬ 
tein  15  per  cent,  carbohydrate  25  per  cent,  fat  50  per  cent,  and  alcohol  10  per 
cent.  To  obtain  the  heat  liberated  in  the  metabolism  of  each  nutrient,  the 

i  Togel,  Brezina,  and  Durig:  Biochem.  Zeitschr.,  1913,  50,  p.  296. 

*  Carpenter:  Carnegie  Inst.  Wash.  Pub.  No.  303a,  1924,  p.  124. 


178 


HUMAN  METABOLISM  WITH  ENEMATA. 


value  for  the  total  metabolism  (2,000  calories)  is  multiplied  by  the  respective 
percentages  assigned  to  the  four  substances.  The  carbon  dioxide  produced 
is  next  calculated  by  dividing  the  calories  obtained  from  each  by  the  calorific 
equivalent  of  1  liter  of  carbon  dioxide,  namely,  5.69  calories  for  protein, 
5.06  calories  for  carbohydrate,  6.72  calories  for  fat,  and  7.28  calories  for  al- 


Table  30. — Amounts  of  carbon  dioxide  'produced,  oxygen  used,  and  heat  liberated  in  the  metab¬ 
olism  of  human  protein,  human  fat,  glycogen,  and  alcohol.  ( 1  gram). 


Substances 

katabolized. 

Carbon 

dioxide. 

Oxygen. 

Heat. 

Calorific  equiva¬ 
lent  of  carbon 
dioxide  per  liter 
/  CalsA 

\  coj 

Calorific  equiva¬ 
lent  of  oxygen 
per  liter 
/  CalsA 

\oJ 

liters. 

liters. 

cals. 

cals. 

cals. 

Human  protein.  . .  . 

0.7738 

0.9569 

4.40 

5.69 

4.60 

Human  fat . 

1.4204 

1 . 9908 

9.54 

6.72 

4.79 

Glycogen . 

.8293 

.8293 

4.20 

5.06 

5.06 

Alcohol . 

.9729 

1.4595 

7.08 

7.28 

4.85 

cohol.  (See  table  30.)  The  results  added  together  give  the  total  volume  of 
carbon  dioxide  produced  in  the  metabolism,  i.  e.,  327.81  liters.  The  oxygen 
used  in  the  combustion  is  likewise  calculated  by  dividing  the  calories  from 
each  material  by  the  calorific  value  for  1  liter  of  oxygen,  these  values  being 
protein  4.60  calories,  carbohydrate  5.06  calories,  fat  4.79  calories,  and  alcohol 
4.85  calories.  The  sum  of  the  results  represents  the  total  volume  of 
oxygen  used — 414.04  liters.  The  respiratory  quotient  and  the  calorific 
equivalents  are  then  readily  calculated. 

Table  31. — Illustrative  calculation  of  respiratory  quotient  and  calorific  values  of  oxygen  and 

carbon  dioxide  with  changing  proportion  of  nutrients. 

[Total  calories  =  2,000.  Derived  from  protein,  15  p.  ct.;  from  carbohydrate,  25  p.  ct. ;  from  fat 

50  p.  ct.;  from  alcohol,  10  p.  ct.] 


Nutrients 

katabolized. 

Heat  produced. 

Carbon  dioxide 
produced. 

Oxygen  absorbed. 

cals. 

liters. 

liters. 

Protein . 

15X2,000=  300 

3004-5.69=  52.72 

3004-4.60=  65.22 

Carbohydrate . 

25X2,000=  500 

5004-5.06=  98.81 

5004-5.06=  98.81 

Fat . 

50X2,000=1,000 

1,0004-6.72  =  148.81 

1,0004-4.79  =  208.77 

Alcohol . 

10X2,000=  200 

2004-7.28=  27.47 

2004-4.85=  41.24 

Total . 

2,000 

327.81 

414.04 

Respiratory  quotient  =  327 . 81  4-414 . 04  =  0.792. 

Calorific  value  of  carbon  dioxide  =  2,000  4- 327.81  =  6.101  cals,  per  liter. 
Calorific  value  of  oxygen  =  2,000 -4- 414.04  =  4.830  cals,  per  liter. 


The  calculations  by  this  method  for  variations  in  replacement  by  alcohol  of 
the  different  nutrients  in  the  metabolism  are  summarized  in  table  32.  In  the 
first  column  of  this  table  is  given  the  respiratory  quotient  for  the  original 
distribution  of  the  metabolism  as  indicated  in  the  following  three  columns. 
Thus,  in  the  first  instance  given,  with  heat  produced  from  the  metabolism  of 


UTILIZATION  OF  ALCOHOL. 


179 


10  per  cent  of  protein,  30  per  cent  of  fat,  and  60  per  cent  of  carboyhdrate, 
the  respiratory  quotient  would  be  0.891.  The  fifth  column  shows  the 
changed  conditions  in  that  alcohol  replaces  the  nutrients  named  in  a  certain 
proportion  (1  per  cent)  of  the  metabolism.  If  more  than  one  nutrient  is 
replaced,  as  in  the  first  case,  the  apportionment  of  the  substitution  is  made 
according  to  the  original  distribution.  In  the  last  column  the  changes  in 
the  respiratory  quotients  are  given  for  the  new  distribution  of  metabolism, 
the  new  quotients  being  lower  than  the  original  quotients  as  a  result  of  the 
replacement  by  alcohol  of  1  per  cent  of  the  total  energy  originally  supplied 
by  the  other  nutrients. 


Table  32. — Theoretical  effect  upon  the  respiratory  quotient  when  alcohol  replaces  one  or  more 

nutrients  in  1  per  cent  of  the  metabolism. 


Initial 

respiratory 

quotient. 

Initial  percentage  distribution 
of  heat  from — 

Alcohol 

Change  in 
respiratory 
quotient 
for  1  p.  ct. 
replacement. 

Protein. 

Fat. 

Carbohydrate. 

A  UpidbblJ 

0.891 

10 

30 

60 

P.  F.  C. 

-0.00224 

.925 

0 

25 

75 

C.  F. 

-  .00259 

.853 

0 

50 

50 

C.  F. 

-  .00186 

.925 

0 

25 

75 

F. 

-  .00044 

.853 

0 

50 

50 

F. 

-  .00046 

.853 

0 

50 

50 

C. 

-  .00327 

.824 

15 

50 

35 

C. 

-  .00320 

.796 

15 

60 

25 

C. 

-  .00320 

.853 

15 

40 

45 

C. 

-  .00324 

.881 

15 

30 

55 

C. 

-  .00325 

.910 

15 

20 

65 

C. 

-  .00326 

Table  32  brings  out  several  points.  If  carbohydrate  alone  is  replaced  by 
alcohol  when  the  initial  combination  is  either  fat  and  carbohydrate,  or  pro¬ 
tein,  fat,  and  carbohydrate,  the  lowering  of  the  respiratory  quotient  due  to  a 
1  per  cent  replacement  by  alcohol  is  about  the  same  (0.00320  to  0.00327), 
regardless  of  the  initial  percentage  of  energy  derivable  from  carbohydrate. 
Accordingly,  if  alcohol  replaces  carbohydrate  alone,  the  fall  in  the  quotient 
with  a  1  per  cent  replacement  of  energy  would  be  the  same,  regardless  of  the 
initial  quotient.  Now,  the  experiments  of  Higgins,  as  well  as  many  of  the 
experiments  in  this  publication,  indicate  that  the  higher  the  initial  respira¬ 
tory  quotient,  the  greater  is  the  fall  due  to  the  ingestion  of  alcohol.  If  the 
view  is  accepted  that  alcohol  replaces  carbohydrate  only,  these  findings 
would  indicate  that  the  replacement  is  greater  with  a  high  proportion  of 
carbohydrate  in  the  total  metabolism  than  when  the  proportion  of  carbo¬ 
hydrate  is  low.  The  experiments  of  Togel,  Brezina,  and  Durig1  favor  this 
view.  They  found  either  that  the  rise  of  the  respiratory  quotient  due  to 
dextrose  and  levulose  was  entirely  suppressed  or  there  was  an  abrupt  low¬ 
ering  as  soon  as  alcohol  was  given.  It  is  popularly  believed  that  the  individ¬ 
ual  accustomed  to  the  use  of  alcohol  does  not  care  for  sweets,  but  that  when 
he  is  deprived  of  alcohol  he  begins  to  crave  them.  Although  such  evidence 
is  unscientific,  it  is  well  to  keep  this  belief  in  mind  in  connection  with  the 
actual  experimental  results  so  far  as  change  in  the  respiratory  quotient  due 
to  the  ingestion  of  alcohol  is  concerned. 


1  Togel,  Brezina,  and  Durig:  Biochem.  Zeitschr.,  1913,  50,  p.  296. 


180 


HUMAN  METABOLISM  WITH  ENEMATA. 


An  examination  of  the  changes  when  alcohol  replaces  fat  alone  shows  much 
less  effect  upon  the  respiratory  quotient  than  when  alcohol  replaces  carbohy¬ 
drate.  Furthermore,  as  with  carbohydrate  alone,  the  original  distribution  of 
energy-producing  material  does  not  affect  particularly  the  lowering  of  the 
quotient  due  to  replacement  of  fat  by  alcohol.  When,  however,  carbohy¬ 
drate  and  fat  are  replaced  by  alcohol  in  their  original  proportions,  that  is,  the 
ratio  of  carbohydrate  to  fat  is  kept  the  same,  but  the  amount  of  energy 
derived  from  the  two  is  lowered,  it  is  found  that  the  lower  the  amount  of 
carbohydrate  at  the  beginning,  the  less  the  quotient  is  lowered  in  the 
replacement  by  alcohol.  This  is  an  application  in  another  way  of  the 
Rosemann  idea,  except  that  protein  is  not  included. 

One  may  calculate  from  this  table  the  probabilities  for  change  in  quotient. 
The  majority  of  the  preliminary  respiratory  quotients  in  the  alcohol  experi¬ 
ments  in  this  research  averaged  between  0.79  and  0.82.  If  we  take,  for  ex¬ 
ample,  a  fall  in  the  respiratory  quotient  of  0.05  and  assume  that  the  change 
was  entirely  due  to  a  replacement  of  fat,  then  the  percentage  of  the  total 
energy  which  would  be  derived  from  alcohol  in  such  replacement  would  be 
equal  to  0.05  divided  by  0.00045  (the  average  change  in  quotient  under  these 
conditions  shown  in  table  32).  This  would  amount  to  111  per  cent,  which  is 
of  course  impossible,  and  this  calculation  therefore  eliminates  the  probability 
of  the  replacement  of  fat  alone  by  alcohol.  If  carbohydrate  only  were  re¬ 
placed  by  alcohol,  with  a  lowering  of  0.05  in  the  respiratory  quotient,  the 
percentage  of  the  total  metabolism  replaced  would  be  0.05  divided  by  the 
average  change  in  quotient  shown  in  table  32  with  such  replacement  (0.00324) 
which  would  give  a  replacement  of  15.4  per  cent.  If  carbohydrate  and  fat 
were  replaced  in  the  proportion  in  which  they  were  being  metabolized,  then 
with  a  lowering  of  0.05  in  the  respiratory  quotient,  the  percentage  replacement 
would  depend  upon  the  previous  combination,  that  is,  the  greater  the  amount 
of  carbohydrate  present,  the  greater  would  be  the  percentage  replacement  for 
each  0.01  change  in  the  respiratory  quotient.  As  previously  stated,  Higgins1 
found  that  the  higher  the  initial  quotient,  the  greater  was  the  fall  when  alcohol 
was  given,  and  the  experiments  in  this  research  show  the  same  tendency. 

In  order  to  have  the  same  rate  of  utilization,  regardless  of  the  original 
composition,  there  would  have  to  be  a  greater  fall  with  a  high  respiratory 
quotient  if  a  combination  of  fat  and  carbohydrate  were  utilized  before  alcohol 
was  given.  However,  if  it  were  true  that  alcohol  burned  at  a  uniform  rate, 
regardless  of  the  proportions  of  other  materials,  it  would  differ  entirely  from 
the  others.  It  has  been  definitely  shown  that  the  higher  the  proportion  of 
carbohydrate  in  the  diet,  the  higher  the  respiratory  quotient  in  a  basal  con¬ 
dition  is,  and  it  is  likewise  well  known  that  the  metabolism  level  of  protein  is 
governed  by  the  protein  intake.  It  therefore  does  not  seem  logical  to  con¬ 
clude  that  alcohol  is  utilized  at  the  same  rate,  independent  of  the  quantity 
taken  in  and  independent  of  the  proportions  of  the  three  nutrients  being 
metabolized  before  its  introduction.  It  seems  more  logical  to  conclude  that 
alcohol  replaces  carbohydrate  in  preference  to  the  other  two  nutrients,  fat 
and  protein. 

The  question  as  to  whether  alcohol  replaces  protein  or  spares  it  is  much 
debated.  Rosemann  2  summarizes  the  findings  on  this  problem  up  to  the 


1  Higgins:  Journ.  Pharm.  and  Exp.  Therapeutics,  1917,  9,  p.  467. 

2  Rosemann:  Oppenheimer’s  Handbuch  d.  Biochem.,  1911,  4,  (1),  p.  434. 


UTILIZATION  OF  ALCOHOL. 


181 


time  of  his  publication,  and  the  evidence  is  conflicting  as  to  whether  the 
utilization  of  protein  is  actually  diminished  or  increased  by  alcohol.  In  our 
experiments  the  giving  of  alcohol  did  not,  apparently,  cause  a  marked  de¬ 
crease  of  nitrogen  in  the  urine  or  an  increase  in  spite  of  the  marked  increase 
in  the  volume  of  urine  which  would  give  ideal  conditions  for  washing  out 
nitrogenous  end  products  of  protein  metabolism.  The  decrease  was  not  so  ap¬ 
parent  as  with  other  substances,  particularly  levulose.  It  is  therefore  question¬ 
able  whether  in  the  calculations  it  should  be  assumed  that  the  protein 
metabolism  is  reduced  by  alcohol.  Experiments  are  needed  in  which  both 
the  nitrogen  output  and  the  sulphur  output  are  determined  in  short  periods 
after  the  ingestion  of  alcohol.  In  our  calculations  it  will  be  assumed  that 
the  course  of  the  protein  metabolism  is  unchanged  by  the  ingestion  of  alcohol. 
In  fact,  it  would  be  impracticable  to  calculate  the  change  in  the  protein 
metabolism,  as  the  urine  was  not  collected  immediately  before  and  im¬ 
mediately  after  the  alcohol  was  given. 

It  is  difficult  to  choose  between  the  two  theories  (1)  whether  alcohol  re¬ 
places  carbohydrate  only  or  (2)  whether  it  replaces  both  fat  and  carbohy¬ 
drate.  Comparison  experiments  are  needed  in  which  the  initial  levels  of  the 
metabolism  vary  as  indicated  by  the  respiratory  quotient  and  in  which  after 
the  ingestion  of  alcohol  the  concentration  of  alcohol  in  the  blood  and  urine  is 
followed  periodically  until  the  alcohol  disappears.  If  alcohol  replaces  car¬ 
bohydrate  only,  then  when  the  combustion  is  essentially  carbohydrate  there 
should  be  a  more  rapid  utilization  of  alcohol  than  when  the  initial  respiratory 
quotient  is  low.  In  experiments  of  this  character  it  should  be  remembered 
that  when  the  respiratory  quotient  is  high,  there  is  a  natural  tendency  for  it 
to  fall,  so  the  individual  should  be  in  such  condition,  as  shown  by  repeated 
tests,  that  the  respiratory  quotient  will  remain  at  a  high  level  over  a  period  of 
several  hours. 

Rosemann’s  formula  assumes  that  after  alcohol  ingestion  the  metabolism 
of  the  three  groups  of  materials  proceeds  in  the  same  proportion  to  one  an¬ 
other  as  before  the  taking  of  alcohol.  Higgins,  in  using  the  formula,  as¬ 
sumed  that  this  applied  only  to  fat  and  carbohydrate.  Such  an  assumption, 
however,  makes  very  little  difference  in  the  calculation,  because  the  respira¬ 
tory  quotient  of  protein  is  between  carbohydrate  and  fat.  The  highest  cal¬ 
culated  combustion  of  alcohol  in  Higgins’s  experiments  was  6.3  grams  per 
hour,  which  gives  a  respiratory  exchange  due  to  alcohol  of  102  c.  c.  of  carbon 
dioxide  and  152  c.  c.  of  oxygen  per  minute;  this  is  54  per  cent  of  the  total 
oxygen  used  in  the  period. 

The  amounts  of  alcohol  theoretically  utilized  have  been  calculated  and  are 
given  in  table  33.  The  experiments  selected  for  the  calculation  are  those  in 
which  the  fall  in  the  respiratory  quotient  due  to  the  injection  of  alcohol  was 
most  positive.  The  calculation  has  been  made  in  two  ways.  In  the  first, 
the  Rosemann  formula  has  been  used  and  the  assumption  made  that  the  alco¬ 
hol  replaces  the  nutrients  in  the  proportion  in  which  they  were  being  uti¬ 
lized  before  the  alcohol  was  taken.  In  our  calculation  no  account  is  made  of 
the  protein,  this  being  in  accord  with  the  custom  of  the  Nutrition  Laboratory 
in  the  calculation  of  total  metabolism  from  the  respiratory  quotient.  The 
neglect  of  the  protein  in  the  calculation  does  not  introduce  a  considerable 
error  as  from  the  theoretical  quotient  of  protein  it  can  be  seen  that  it  is  prac¬ 
tically  an  average  of  the  other  two  quotients,  that  is,  the  quotient  of  protein 


182 


HUMAN  METABOLISM  WITH  ENEMATA. 


is  0.81,  while  the  quotients  of  fat  and  carbohydrate  are  0.70  and  1.00,  respec¬ 
tively.  In  the  calculation  by  the  Rosemann  formula,  it  was  also  assumed 
that  the  oxygen  absorption  remained  unchanged  after  alcohol  ingestion. 
This  is  not  strictly  true,  as  in  a  number  of  cases,  particularly  in  the  night  ex¬ 
periments  with  a  7.5  per  cent  alcohol  solution,  there  was  a  noticeable  increase 
in  the  oxygen  absorption. 


Table  33. — Calculated  amounts  of  alcohol  used  per  hour. 


Respiratory  quotient. 

Alcohol 

Percent¬ 
age  of 

Volume 
of  in¬ 
jection. 

After  injection. 

Oxygen 

absorp¬ 

tion 

per 

minute.0 

Alcohol 
used 
per  hour 
(calcu¬ 
lated).6 

used 

per  hr.,  if 
carbohy¬ 
drate 
alone  is 
replaced 
(calcu¬ 
lated). 

Date. 

alcohol 
in  solu¬ 
tion,  and 
subject. 

Before 

injec¬ 

tion. 

Time  of 
minimum 
from  be¬ 
ginning  of 
injection. 

Average 

mini¬ 

mum 

quotient. 

1915. 

Oct.  24 

5  p.  ct. 

C 

c.  c. 

325 

0.79 

hrs. 

2  to  2$ 

0.75 

c.  c. 
275 

grams. 

3.7 

grams. 

1.4 

Nov.  18 

A 

400 

.81 

3 

4 

1  4 

.78 

195 

1.7 

0.7 

Nov.  24 

A 

420 

.86 

H 

2 

.78 

200 

3.5 

2.1 

Dec.  2 

A 

420 

.88 

1 

3 

.79 

215 

3.8 

2.5 

1916. 

Feb.  18 

D 

520 

.81 

2 

3 

.78 

235 

2.0 

0.9 

Apr.  17 

A 

1,020 

.80 

34 

5 

.76 

205 

2.6 

1.0 

Feb.  28 

7.5  p.  ct. 
A 

265 

.82 

24 

34 

.76 

200 

3.3 

1.5 

Mar.  3 

D 

265 

.80 

31 

4 

.76 

235 

3.0 

1.2 

Apr.  10 

A 

350 

.83 

44 

.77 

200 

3.1 

1.5 

Apr.  15 

A 

500 

.83 

2 1 

34 

.75 

212 

4.4 

2.2 

1917. 

Jan.  20-21 

A 

500 

.81 

H 

24 

.76 

200 

3.0 

1.3 

Feb.  3-  4 

A 

500 

.87 

34 

54 

.77 

200 

4.1 

2.6 

Feb.  15-16 

A 

500 

.87 

14 

24 

.78 

205 

3.8 

2.4 

Mar.  23-24 

A 

500 

.83 

34 

4 

.76 

220 

4.0 

2.0 

1916. 

Mar.  6 

10  p.  ct. 
A 

265 

.81 

2 

24 

.76 

225 

3.3 

1.4 

Mar.  8 

C 

265 

.82 

2 

24 

.77 

270 

3.7 

1.7 

Mar.  10 

D 

265 

.83 

14 

24 

.76 

220 

4.0 

2.0 

°  Oxygen  at  time  of  minimum  quotient.  6  Rosemann’s  formula  used. 


In  the  second  method  of  calculation  it  was  assumed  that  the  alcohol 
replaced  carbohydrate  alone  and  the  theoretical  values  in  table  32  used. 
According  to  this  table,  when  carbohydrate  alone  is  replaced  and  the  re¬ 
spiratory  quotient  approximates  0.79  to  0.82,  the  theoretical  replacement  of 
1  per  cent  of  the  energy  production  by  alcohol  results  in  lowering  the 
respiratory  quotient  0.00320.  The  details  of  this  second  method  of  calcula¬ 
tion  were  as  follows:  The  total  heat-production  was  calculated  by  utilizing 
the  oxygen  absorption  and  the  calorific  value  of  oxygen  at  the  respiratory 
quotient  before  injection.  The  difference  between  the  average  respiratory 
quotient  before  injection  and  the  average  minimum  quotient  after  injection 
was  then  divided  by  the  theoretical  value  for  replacement  of  1  per  cent  of 
the  energy  from  carbohydrate  by  alcohol,  namely,  0.00320.  This  gave  the 
percentage  of  the  total  metabolism  which  was  replaced  by  alcohol.  Mul¬ 
tiplying  the  heat-production  by  this  percentage  gave  the  heat  derived  from 
alcohol.  The  calories  derived  from  alcohol  were  then  divided  by  the  factor 


UTILIZATION  OF  ALCOHOL. 


183 


7.08  (see  table  30)  and  multiplied  by  60  to  obtain  the  grams  of  alcohol 
utilized  per  hour  when  carbohydrate  alone  was  replaced. 

The  amounts  of  alcohol  theoretically  utilized,  as  calculated  by  the  first 
method,  i.  e.,  with  the  Rosemann  formula,  which  assumes  the  replacement  of 
all  the  nutrients  by  alcohol,  are  given  in  the  next  to  the  last  column  of  the 
table.  The  amounts  vary  from  1.7  to  4.4  grams  per  hour.  In  general,  the 
amounts  utilized  per  hour  with  a  5  per  cent  alcohol  solution  are  slightly  lower 
than  those  with  a  7.5  per  cent  alcohol  solution,  but  it  must  be  noted  that  the 
quantities  of  alcohol  actually  injected  were,  in  general,  somewhat  larger  with 
the  7.5  per  cent  solution  than  with  the  5  per  cent  solution.  The  amounts 
per  hour  with  the  10  per  cent  solution  are  of  about  the  same  order  as  with  the 
7.5  per  cent  solution  although  the  quantities  of  alcohol  injected  were  26.5 
grams  as  compared  with  37.5  grams  in  the  last  five  experiments  with  the  7.5 
per  cent  solution.  According  to  these  calculations  from  the  respiratory 
quotient,  therefore,  the  amounts  utilized  per  hour  are  essentially  the  same, 
regardless  of  the  amounts  of  alcohol  injected.  This  finding  corresponds 
with  that  given  by  Higgins. 

The  highest  values  for  alcohol  utilized  approach  somewhere  near  the  values 
computed  from  the  disappearance  of  alcohol  in  the  urine.  (See  p.  174.)  The 
conclusion  was  drawn  from  the  urine  determinations  that  25  grams  of  alcohol 
disappeared  in  about  5  hours.  This  would  correspond  to  about  5  grams  per 
hour.  The  maximum  figure  shown  in  table  33  is  4.4  grams  per  hour.  At 
the  maximum  rate  of  utilization  of  4.4  grams  per  hour,  it  would  take  over  8 
hours  for  the  37.5  grams  of  alcohol  given  in  this  experiment  to  be  completely 
utilized.  In  the  experiments  which  were  continued  through  the  night  there 
was  no  indication  of  a  return  to  the  original  respiratory  quotient,  even  after 
6  hours.  Experiments  are  needed  to  confirm  the  general  idea  that  these 
rates  as  calculated  really  represent  the  rate  of  utilization.  If  the  experi¬ 
ments  had  been  sufficiently  long,  they  ought  to  have  shown  that  at  the  end  of 
5  to  8  hours  there  was  a  tendency  for  the  quotient  to  return  to  a  level 
approximately  that  before  injection  took  place. 

The  figures  in  the  last  column  show  the  theoretical  values  when  the  alcohol 
replaces  only  carbohydrate.  In  general,  these  values  are  much  lower,  most 
of  them  being  less  than  one-half  of  those  in  the  column  preceding.  Ac¬ 
cordingly,  if  one  assumes  that  the  alcohol  replaces  carbohydrate  alone,  the 
time  of  utilization  would  be  much  longer  than  when  it  is  assumed  that  the 
alcohol  replaces  all  the  nutrients.  From  this  comparison,  and  considering 
also  the  time  of  the  disappearance  of  alcohol  from  the  urine,  it  would  appear 
that  Rosemann’s  assumption  was  correct,  namely,  that  alcohol  replaces  the 
nutrients  in  the  proportion  in  which  they  were  being  utilized  before  alcohol 
was  taken.  As  pointed  out  before,  alcohol  must  therefore  behave  differently 
from  any  other  material  used  as  food.  The  investigation  on  the  concen¬ 
tration  of  alcohol  in  the  bodies  of  fowls  after  its  inhalation1  indicates  that 
alcohol  may  serve  as  a  source  of  energy  for  muscular  work. 

The  time  of  the  lowest  quotient  after  alcohol  injection  is  given  in  the  fifth 
column  and  varies  from  1  to  3§  hours.  This  is  simply  the  expression  of  the 
time  when  the  greatest  change  took  place  as  compared  with  the  quotient 
before  injection,  and  should  not  be  confused  with  the  time  when  the  earliest 
change  in  the  respiratory  quotient  took  place.  In  some  cases  it  will  be  seen 

Carpenter  and  Babcock:  Amer  Jour.  Physiol.,  1919,  49,  p.  128. 


1* 


184 


HUMAN  METABOLISM  WITH  ENEMATA. 


that  it  corresponds  very  closely  to  the  peak  of  concentration  of  alcohol  in  the 
urine  and  in  other  cases  it  is  somewhat  later. 

The  general  conclusion  from  this  theoretical  calculation  is  that  not  over  5 
grams  of  alcohol  are  actually  utilized  per  hour,  irrespective  of  the  quantity 
injected,  and  that  this  value  corresponds  fairly  closely  to  the  conclusions 
drawn  from  the  urine  analyses. 

The  maximum  theoretical  percentage  of  the  total  metabolism  which  can  be 
replaced  by  alcohol  is  shown  by  the  following  calculation:  In  the  experiment 
with  A  on  April  15,  1916,  the  oxygen  absorption  before  injection  was  212  c.  c. 
per  minute  which,  with  a  respiratory  quotient  of  0.83,  gives  a  heat-produc¬ 
tion  of  61.5  calories  per  hour.  The  alcohol  theoretically  utilized  in  this 
experiment  is  shown  in  table  33  to  be  4.4  grams,  which,  at  7.08  calories  per 
gram,  gives  31.2  calories,  or  51  per  cent  of  the  total  heat-production.  This  is 
in  good  agreement  with  the  values  found  by  Higgins  with  oral  ingestion,  who 
gives  54  per  cent  as  the  maximum  utilization  of  oxygen  in  the  combustion  of 
alcohol,  which  corresponds  very  closely  with  the  percentage  heat-production. 
It  would  thus  appear  that  the  percentage  of  the  total  metabolism  replaceable 
by  alcohol  is  about  the  same,  regardless  of  whether  the  alcohol  is  given  by 
rectum  or  by  mouth. 

An  anomaly  brought  out  by  a  comparison  of  the  respiratory  exchange  with 
the  concentration  of  alcohol  in  urine  is  that,  according  to  the  urine  values,  the 
highest  theoretical  utilization  of  alcohol  was  observed  about  lj  to  2  hours 
after  ingestion,  but  according  to  the  respiratory  exchange  it  would  appear 
that  the  highest  utilization  of  alcohol  was  somewhat  later  than  this,  particu¬ 
larly  in  the  night  experiments,  in  which  the  respiratory  quotient  continued 
to  fall  throughout  the  night.  The  urine  figures  indicate  the  disappearance 
of  alcohol  from  the  body,  but  if  this  were  true,  then  the  respiratory  quotient 
would  begin  to  rise  to  indicate  a  return  to  previous  conditions,  but  it  does  not. 

The  lack  of  consistency  between  the  evidence  supplied  by  the  respiratory 
exchange  and  that  of  the  urine  determinations  suggests  the  need  of  further 
investigation,  particularly  if  arrangements  can  be  made  for  simultaneous 
determinations  of  the  alcohol  concentration  in  the  blood  and  urine  and  of  the 
respiratory  exchange.  The  experiments  of  Strassmann  1  indicate  that  the 
determination  of  the  amount  of  alcohol  in  the  expired  air  would  likewise  be  of 
value  as  showing  the  course  of  the  disappearance  of  alcohol  from  the  body. 
Strassmann  found  that  after  the  taking  of  from  50  to  60  c.  c.  of  alcohol,  an 
average  of  2.06  c.  c.  of  alcohol  were  eliminated  in  the  expired  air  in  the  first 
hour,  1.49  c.  c.  in  the  second  hour,  with  diminishing  amounts  in  the  succeed¬ 
ing  hours,  only  0.6  gram  being  eliminated  in  the  breath  during  the  fourth 
hour.  These  were  much  larger  amounts  than  were  found  by  Atwater  and 
Benedict 2  with  individual  doses  much  smaller  and  more  dilute. 

Simultaneous  studies  of  the  respiratory  exchange  and  the  amount  of 
alcohol  in  the  expired  air  would  be  of  value  in  correlating  the  change  in 
alcohol-content  of  the  body  with  the  respiratory  exchange. 

As  brought  out  in  previous  discussion,  the  experiments  on  rectal  feeding 
indicate  that  the  proportion  of  the  total  metabolism  due  to  the  alcohol 
injected  may  be  as  high  as  51  per  cent.  The  utilization  of  alcohol  in  rectal 
feeding  therefore  plays  a  prominent  role  in  the  total  metabolism. 

1  Strassmann:  Arch.  f.  Physiol.,  1891,  49,  p.  315. 

2  Atwater  and  Benedict:  National  Acad.  Sci.,  1902,  8,  6th  mem.,  p.  393,  table  122. 


UTILIZATION  OF  DEXTROSE. 


185 


Utilization  of  Dextrose  When  Introduced  Rectally. 

The  utilization  of  dextrose  is  discussed  in  much  the  same  manner  and  from 
the  same  standpoint  as  the  utilization  of  alcohol.  The  absorption  studies 
show  conclusively  that  it  was  not  possible  to  recover  any  considerable 
amount  of  dextrose  when  introduced  into  the  rectum  in  a  0.6  per  cent  solu¬ 
tion  of  sodium  chloride,  if  the  attempt  were  made  within  3  or  4  hours.  For¬ 
tunately,  in  all  of  the  absorption  experiments,  more  than  one  wash-out  was 
given  at  the  end  of  the  experiment,  and  the  second  was  of  such  size  that  the 
removal  of  the  unabsorbed  material  should  be  fairly  complete.  This  is 
shown  by  the  fact  that  in  a  number  of  instances  the  amount  of  dextrose  that 
was  actually  present  in  the  second  wash-out  was  0,  while  in  other  cases  the 
amount  obtained  was  a  very  small  percentage  of  the  total  amount  recovered. 
The  actual  amount  in  the  second  wash-out  ranged  from  4.2  grams  to  0.  A 
third  wash-out  was  given  on  two  occasions.  In  one  no  unabsorbed  dextrose 
was  found,  and  in  the  other  but  0.9  gram  of  the  30  grams  introduced.  Ap¬ 
parently,  therefore,  the  absorption  from  30  grams  was  17.5  to  26.3  grams. 

It  may  be  suggested  that  this  disappearance  was  due  to  a  fermentation 
which  takes  place  in  the  colon  and  rectum.  No  attempts  were  made  in  these 
studies  to  determine  whether  fermentation  had  any  part  in  the  disappearance 
of  the  dextrose  injected.  Studies  of  such  character  have  been  made  by  pre¬ 
vious  investigators,  however,  from  which  they  have  concluded  that  while  a 
small  amount  of  fermentation  may  actually  take  place  (considered  as  lactic- 
acid  fermentation  by  Mutch  and  Ryffel),1  the  material  is  actually  absorbed. 
This  conclusion  is  corroborated  in  some  of  the  studies  by  observations  of  the 
blood-sugar  which  showed  a  slight  increase,  thus  supplying  evidence  that  the 
utilization  is  fulfilled  by  actual  absorption  into  the  circulation  of  the  dextrose 
introduced. 

The  studies  upon  the  composition  and  amount  of  the  urine  show  that  in  a 
number  of  cases  the  volume  was  increased  after  the  injection  of  a  500  c.  c. 
solution  of  dextrose,  while  in  others  it  was  decreased;  consequently,  there  was 
no  general  directional  effect  as  to  change  in  volume.  The  nitrogen  in  the 
urine  changed  on  the  average  =*=  25  per  cent,  but  when  averaged  with  refer¬ 
ence  to  sign,  there  was  a  directional  change  of  — 13  per  cent,  indicating  a 
slight  decrease  in  nitrogen  output.  This,  however,  is  hardly  significant 
enough  to  be  considered  as  proof  that  the  injection  of  this  amount  of  dex¬ 
trose  caused  an  actual  sparing  of  the  protein  metabolism. 

The  maximum  change  in  the  respiratory  quotient  after  the  injection  of 
dextrose  solution  occurred  with  subject  A  on  February  22,  1917,  in  an  experi¬ 
ment  with  30  grams  of  dextrose  in  a  520  c.  c.  solution  with  the  subject  inside 
a  respiration  chamber.  The  average  of  the  first  3  or  4  respiratory  quotients 
was  about  0.86;  the  giving  of  the  dextrose  raised  it  to  an  average  in  two  pe¬ 
riods  of  0.92  during  the  sixth  and  seventh  half  hours  after  injection,  that  is, 
about  3  to  3J  hours  after  injection.  In  the  experiment  with  the  same  sub¬ 
ject  on  May  4,  1916,  there  was  a  change  from  about  0.82  to  0.87,  that  is,  an 
increase  of  0.05.  According  to  the  table  of  Williams,  Riche,  and  Lusk,2  a 
change  of  this  magnitude  in  the  respiratory  quotient  results  in  a  change  of 
more  than  15  per  cent  in  the  proportion  of  energy  from  carbohydrate. 


1  Mutch  and  Ryffel:  British  Med.  Journ.,  1913,  l,p.  111.  See,  also,  p.  13  of  this  monograph. 

2  Williams,  Riche,  and  Lusk:  Journ.  Biol.  Chem.,  1912,  12,  p.  357. 


186 


HUMAN  METABOLISM  WITH  ENEMATA. 


As  was  done  for  the  alcohol  experiments,  a  calculation  has  been  made  of 
the  utilization  of  the  material  injected  by  comparing  the  utilization  of  carbo¬ 
hydrate  before  and  after  the  ingestion  of  the  dextrose  solution.  The  compu¬ 
tations  in  this  case,  however,  were  made  from  the  non-protein  respiratory 
quotients.  These  were  obtained  by  deducting  from  the  values  for  carbon 
dioxide  and  oxygen  the  amounts  due  to  protein  alone,  and  the  quotient  found 
by  dividing  the  remainder  for  the  carbon  dioxide  by  that  for  the  oxygen  was 
the  non-protein  respiratory  quotient.  From  the  oxygen  per  minute  thus 
obtained,  the  non-protein  respiratory  quotient  and  the  calories  per  liter  of 
oxygen  corresponding  to  the  respiratory  quotient,1  a  calculation  was  made 
of  the  heat  output  due  to  the  katabolism  of  carbohydrate  and  fat.  The 
amount  due  to  carbohydrate  alone  was  obtained  by  employing  the  table  of 
Williams,  Riche,  and  Lusk.2  This  divided  by  the  heat  produced  in  the  oxi¬ 
dation  of  1  gram  of  dextrose,  namely,  3.74  calories,  gave  the  amount  of  carbo¬ 
hydrate  as  dextrose  utilized  before  injection.  Multiplying  by  60  gave  the 
amount  per  hour.  The  same  method  was  used  for  calculating  the  utilization 
after  injection,  except  that  instead  of  an  average,  the  maximum  respiratory 
quotient  was  taken,  preferably  from  that  portion  of  the  experiment  in  which 
there  was  more  than  one  high  respiratory  quotient.  There  were  only  five 
experiments  which  appear  suitable  for  such  calculation,  and  the  results  of 
these  are  given  in  table  34.  Three  of  the  experiments  were  with  subject  A  and 
two  with  subject  C.  The  amounts  of  carbohydrate  utilized  per  hour  before 
injection  were  4.4,  4.6,  and  7.8  grams  with  A  and  8.9  and  7.3  grams  with  C. 
The  values  for  C  are  larger  for  two  reasons:  one,  because  his  actual  metab¬ 
olism  was  higher,  and  the  other  because  the  respiratory  quotient  tended  to 
be  higher.  After  injection  the  increase  was  greater  with  A  than  with  C, 
the  values  being  8.4,  8.3,  and  11.4  grams  for  A,  with  a  general  increase  of 
about  4  grams,  while  the  values  for  C  were  10.2  and  10.3  grams. 

The  amounts  of  dextrose  apparently  absorbed  in  these  four  experiments 
(see  p.  32)  were  for  A  34.6,  17.5,  and  26.3  grams,  respectively,  while  for  C  they 
were  17.7  and  18.4  grams.  Consequently,  with  A  the  amount  of  dextrose 
actually  utilized  after  injection  would  be  suppliedintwoexperimentsforabout 
2  hours  by  the  amount  absorbed,  and  in  the  other  experiment  for  4  hours,  while 
for  C  the  amount  absorbed  in  both  experiments  would  be  sufficient  for  only 
If  hours.  If  one  considered  only  the  increase  in  utilization  of  carbohydrate, 
then  the  amount  supplied  would  suffice  for  a  much  longer  period  of  time. 
The  experiment  of  April  28,  in  which  double  the  amount  of  dextrose  was 
ingested  (60  grams),  shows  the  desirability  of  injecting  more  than  30  grams  at 
one  time.  The  percentage  increase  in  the  total  metabolism  supplied  by 
carbohydrate  has  been  calculated  for  April  28,  taking  as  an  actual  increase  4 
grams  per  hour,  and  has  been  found  to  be  27  per  cent. 

In  this  discussion  two  experiments  have  been  omitted,  because  a  5 
per  cent  alcohol  solution  was  the  medium  in  which  the  dextrose  was  given, 
and  the  course  of  the  respiratory  quotient  indicates  that  there  is  no  increase 
in  carbohydrate  utilization,  or,  if  there  were  an  increase,  it  was  offset  by  the 
simultaneous  metabolism  of  alcohol.  Other  experiments  have  been  omitted 
because  there  was  no  marked  difference  between  the  average  preliminary 
respiratory  quotient  and  the  maximum  respiratory  quotient.  If,  however, 


1  Carpenter:  Carnegie  Inst.  Wash.  Pub.  No.  303a,  1924,  p.  104. 

2  Williams,  Riche,  and  Lusk,  loc.  cit.;  also,  Carpenter,  loc.  cit.,  p.  104. 


UTILIZATION  OF  LEYULOSE. 


187 


those  experiments  are  included  in  which  there  was  a  positive  difference  be¬ 
tween  the  minimum  and  maximum  respiratory  quotients,  others  might  have 
been  considered,  as,  for  example,  that  of  May  9,  in  which  the  quotients  in  the 
first  hour  after  injection  averaged  materially  lower  than  those  in  the  second 
and  third  hours,  showing  that  there  was  no  apparent  increase  in  the  utiliza¬ 
tion  of  carbohydrate  in  the  hour  immediately  following  injection. 

Table  34. — Carbohydrate  utilization  before  and  after  rectal  injection  of  dextrose  solutions. 


Sub¬ 

ject. 

Date. 

Before  injection. 

After  injection. 

Oxygen 
absorbed 
per  minute.® 

Average  non¬ 
protein  respira¬ 
tory  quotient. 

Proportion  of 
calories  from 
carbohydrate. 

Amount  of  car¬ 

bohydrate  as 
dextrose  uti¬ 

lized  per  hour. 

Oxygen 

absorbed 

per  minute.6 

Maximum 

non-protein 

respiratory 

quotient. 

Proportion  of 

calories  from 

carbohydrate. 

Amount  of  car¬ 

bohydrate  as 
dextrose  uti¬ 

lized  per  hour. 

1916. 

c.  c. 

p.  ct. 

grams. 

c.  c. 

p.  ct. 

grams. 

A 

Apr.  28 

161 

0.81 

35.4 

4.4 

153 

0.91 

69.4 

8.4 

May  4 

169 

.81 

35.4 

4.6 

168 

.89 

62.6 

8.3 

C 

May  11 

234 

.85 

49.0 

8.9 

233 

.87 

55.8 

10.2 

1917. 

Apr.  17 

192 

.85 

49.0 

7.3 

221 

.88 

59.2 

10.3 

A 

Feb.  22 

168 

.88 

59.2 

7.8 

165 

.96 

86.4 

11.4 

°  Oxygen  computed  as  used  in  katabolism  of  carbohydrate  and  fat. 

6  Oxygen  used  in  katabolism  of  carbohydrate  and  fat  as  computed  from  the  oxygen  absorption 
for  maximum  respiratory  quotient. 


The  experiments  as  a  whole  indicate  very  clearly  that  the  effect  of  the 
injection  of  dextrose  solutions  by  rectum  is  to  increase  the  proportion  of 
carbohydrate  being  utilized  and  consequently  to  increase  the  respiratory 
quotient.  The  amount  actually  absorbed  in  these  experiments  would  hardly 
suffice  for  supplying  the  total  carbohydrate  utilization  for  more  than  2  or  3 
hours,  except  in  one  case  when  60  grams  were  given.  The  effect  of  the 
dextrose  solution  upon  the  pulse-rate  was  not  marked  and  was  evident  in  but 
few  of  the  experiments. 

Utilization  of  Levulose  with  Rectal  Introduction.  . 

The  absorption  studies  of  rectal  injection  of  levulose  showed  positive 
results.  As  the  amount  obtained  in  the  second  wash-out  was  considerable 
and  sometimes  higher  than  that  found  in  the  first  wash-out,  it  would  seem  that 
in  many  cases  the  unabsorbed  material  was  not  entirely  removed.  However, 
apparently  the  greater  the  quantity  of  material  injected,  the  larger  was 
the  absorption.  The  absorption  experiments  consequently  showed  that  the 
material  ingested  was  available  for  utilization. 

A  study  of  the  composition  and  volume  of  the  urine  indicates  that  the 
effect  of  levulose  was  somewhat  different  from  that  of  the  sodium-chloride 
solution,  the  alcohol,  or  the  dextrose.  In  the  first  place,  the  changes  in 
volume  of  urine  eliminated  as  compared  with  the  volume  preceding  injection 
were  smaller  percentagewise  than  with  any  of  the  other  materials  studied, 
and  the  liquid  absorbed  must  have  been  retained  rather  than  eliminated. 
Also  the  effect  upon  the  nitrogen  elimination  was  more  positive  with  levulose 
than  with  most  of  the  other  substances,  there  being  a  decrease  in  the  nitrogen 
elimination  of  21  and  28  per  cent  in  the  two  groups  of  levulose  experiments. 


188 


HUMAN  METABOLISM  WITH  ENEMATA. 


This  decrease  can  not  be  assigned  to  a  smaller  elimination  of  urine,  as  the 
volume  excreted  was  either  the  same  or  slightly  greater  after  injection  as 
compared  with  that  before.  It  would  appear  from  this  difference  in  effect 
upon  the  volume  of  urine  that  the  liquid  was  withheld  in  order  to  retain 
the  levulose,  while  on  the  other  hand  the  decrease  in  the  nitrogen  elimination 
would  point  to  a  protective  action  on  the  part  of  the  levulose. 

In  some  of  the  levulose  experiments  there  was  a  positive  change  in  the 
pulse-rate  in  that  it  rose  as  a  result  of  the  injection.  This  is  shown  especially 
in  the  experiments  with  C  on  January  12,  February  1,  7,  and  15.  However, 
there  was  not  in  every  case  a  simultaneous  increase  in  the  respiratory  quo¬ 
tient.  This  finding  is  of  interest  from  the  fact  that  it  indicates  that  levulose 
has  a  stimulating  action  when  introduced  reetally  without  producing  at  the 
same  time  a  metabolic  change  with  consequent  utilization  of  levulose.  Of 
interest  in  this  connection  are  similar  results  obtained  by  Joslin,1  who  found 
in  several  experiments  that  the  levulose  ingested  orally  produced  no  increase 
in  the  respiratory  quotient  and  in  some  cases  there  was  a  fall.  He  also  found2 
an  increased  oxygen  absorption,  a  slight  decrease  in  the  respiratory  quotient, 
and  an  increase  in  the  heart-rate.  His  findings  are  similar  to  some  extent  to 
the  results  here  in  that  there  was  an  increase  in  heart-rate  and  some  increase 
in  oxygen  absorption,  with  no  marked  change  in  the  respiratory  quotient. 

The  majority  of  the  experiments  show  but  little  indication  of  increase  in  the 
carbohydrate  utilization  due  to  the  rectal  injection  of  levulose.  In  one  ex¬ 
periment,  however  (that  with  subject  A  on  January  18,  1916),  there  was  a 
marked  change  in  the  respiratory  quotient.  In  this  experiment  the  subject 
received  50  grams  of  levulose  in  500  c.  c.  of  a  sodium-chloride  solution.  The 
average  respiratory  quotient  before  injection  was  about  0.77,  and  2\  hours 
after  injection  there  were  three  values  which  average  about  0.93,  or  an  increase 
of  0.16.  This  picture  approximates  more  nearly  the  type  of  change  in  the 
respiratory  quotient  when  levulose  is  given  by  mouth  than  that  found  in  any 
other  experiment.  The  subject  reported  in  connection  with  the  experiment 
that  during  the  last  hour  he  had  cramps,  but  this  was  somewhat  later  than 
the  period  of  the  maximum  respiratory  quotient.  In  fact,  from  the  other 
curves  it  would  seem  that  the  maximum  respiratory  quotient  came  before  the 
change  in  heart-rate  and  in  oxygen  absorption.  It  is  rather  difficult  to  ex¬ 
plain  why  in  this  particular  experiment  there  was  such  a  marked  change  in 
the  respiratory  quotient,  which  does  not  appear  in  any  of  the  other  9  experi¬ 
ments.  The  non-protein  respiratory  quotient  for  the  period  before  injection 
was  about  0.76,  and  this,  considering  only  the  non-protein  metabolism,  would 
correspond  to  about  18  per  cent  of  the  katabolism  coming  from  carbohydrate. 
The  non-protein  respiratory  quotient  at  the  period  of  the  highest  quotient 
was  0.95,  which  would  correspond  to  83  per  cent  of  the  non-protein  metab¬ 
olism  coming  from  carbohydrate. 

The  fact  that  the  majority  of  the  experiments  do  not  show  so  positive  a 
rise  in  the  respiratory  quotients  as  one  obtains  when  the  substance  is  given  by 
mouth  would  indicate  that  levulose  was  either  retained  unused  or  that  its 
metabolism  was  of  such  a  character  that  it  did  not  result  in  a  material  change 
in  the  respiratory  quotient,  as,  for  example,  would  result  when  levulose  is  con¬ 
verted  to  glycogen.  The  general  hypothesis  as  to  the  cause  for  the  difference 
in  metabolism  between  mouth  feeding  and  rectal  feeding  follows. 


1  Joslin:  Carnegie  Inst.  Wash.  Pub.  No.  323,  1923,  p.  231. 


2  Ibid,  pp.  302  and  309. 


HYPOTHETICAL  DISCUSSION. 


189 


HYPOTHETICAL  DISCUSSION. 

There  are  two  explanations  usually  offered  for  the  difference  between  the 
results  obtained  with  rectal  feeding  and  with  oral  ingestion.  One  is  that  the 
solutions  introduced  rectally  are  absorbed  in  the  lower  hemorrhoidal  veins 
and  that  as  these  are  not  connected  directly  with  the  portal  system,  therefore 
the  substances  are  introduced  immediately  into  the  general  circulation  and  so 
distributed  throughout  the  body.  In  this  way  the  materials  do  not  come  to 
the  liver  at  once  in  any  quantity,  but  only  indirectly.  The  other  explanation 
is  that  the  character  of  the  results  metabolically  is  due  to  the  slow  absorption 
of  substances  introduced  rectally. 

The  lower  hemorrhoidal  veins  are  situated  in  a  short  section  of  the  rectum 
and  constitute  but  a  very  small  portion  of  the  venous  circulation  of  the  large 
intestine;  the  middle  and  upper  hemorrhoidal  veins  join  the  tributaries  to  the 
portal  circulation.  Consequently,  the  idea  that  absorption  would  take 
place  by  the  lower  hemorrhoidal  veins  alone  would  be  tenable  only  when  the 
other  portions  of  the  venous  circulation  were  closed  off  mechanically,  or 
when  the  volume  of  the  solution  injected  was  so  small  that  it  could  not  reach 
the  middle  and  upper  portions  of  the  colon.  There  have  been  some  experi¬ 
ments  in  which  a  separation  has  been  made,  and  in  one  of  these  glycosuria 
was  produced,  the  only  instance  in  which  it  has  occurred  with  rectal  feeding. 
The  subjective  impressions  of  our  men  would  lead  one  to  believe  very 
strongly  that  the  solutions  generally  passed  well  up  into  the  transverse  colon. 
Furthermore,  Case  has  shown  by  X-ray  that  quantities  of  1,000  c.  c.  or  over 
always  pass  to  the  cecum.  In  fact,  one  of  the  much  discussed  questions  in 
rectal  injection  is  whether  the  ileocecal  valve  is  “  patent,”  i.  e.,  open,  and 
whether  the  material  is  absorbed  because  it  gets  beyond  the  cecum  into  the 
small  intestine.  In  view  of  these  facts  it  does  not  seem  logical  to  accept  the 
theory  that  substances  injected  rectally  are  absorbed  solely  in  the  lower 
hemorrhoidal  veins. 

Some  observations  in  a  recent  study  by  Levy1  on  rectal  introduction  of 
digitalis  have  a  bearing  on  the  question  as  to  how  far  solutions  penetrate  and 
from  what  part  of  the  intestine  absorption  takes  place.  Levy  administered 
rectally  aqueous  solutions  of  digitalis  in  volumes  of  8  to  20  c.  c.,  which  were 
washed  in  with  25  c.  c.  of  water.  In  a  discussion  of  the  anatomy  of  the  large 
intestine,  he  comes  to  the  conclusion  that  only  a  very  small  portion  of  the 
venous  circulation  connects  directly  with  the  systemic  circulation,  so  that  in 
order  to  agree  with  the  general  concept  that  the  results  of  rectal  feeding  are 
due  to  direct  entrance  into  the  systemic  circulation,  one  would  have  to  believe 
that  absorption  took  place  in  the  lower  part  of  the  rectum  only. 

Levy  conducted  a  series  of  tests  to  determine  the  depth  to  which  solutions 
penetrated  and  the  place  where  absorption  took  place.  He  injected  by 
rectal  tube  20  c.  c.  of  a  15  per  cent  solution  of  sodium  iodide,  washed  through 
with  25  c.  c.  of  water.  He  then  made  roentgenograms  of  the  abdomen  15 
minutes,  2,  4,  and  6  hours  after  injection.  With  three  patients  some  of  the 
solution  was  visible  in  the  rectum  immediately  after  it  had  been  given,  but 
most  of  it  was  in  the  lower  sigmoid.  With  two  of  these  cases  some  of  the 
iodide  could  be  seen  as  high  up  as  the  splenic  flexure.  With  the  fourth 
patient  all  of  the  iodide  was  in  the  sigmoid.  With  three  cases  it  had  disap- 


1  Levy:  Ao-ch.  Intern.  Med.,  1924,  33,  pp.  742-757. 


190 


HUMAN  METABOLISM  WITH  ENEMATA. 


peared  in  from  4  to  6  hours,  and  with  the  fourth  a  considerable  amount  was 
still  present  in  the  sigmoid  and  upper  rectum  5  hours  after  injection.  Iodide 
was  also  given  in  smaller  quantities  to  two  other  patients,  15  c.  c.  of  iodide 
solution  being  washed  in  with  15  c.  c.  of  water.  Again,  although  some  was 
seen  in  the  rectum,  most  of  the  solution  passed  into  the  distal  loops  of  the 
sigmoid.  Absorption  was  complete  in  4  to  5  hours. 

Levy  comes  to  the  conclusion  that  most  of  the  digitalis  given  by  rectum  is 
taken  into  the  venous  circulation  by  the  mesenteric  and  portal  systems.  He 
found  that  the  effects  of  rectal  digitalis  therapy  appeared  at  about  the  same 
time  as  similar  doses  by  mouth,  and  concludes  that  the  absorption  rate  of 
digitalis  is  about  the  same  by  rectal  injection  as  by  oral  ingestion. 

The  idea  that  substances  when  rectally  introduced  are  absorbed  so  slowly 
as  to  cause  smaller  changes  in  metabolism  than  when  introduced  by  mouth 
has  more  ground  for  belief.  Absorption  is  slow,  particularly  with  reference 
to  sugars,  but  the  curves  for  the  concentration  of  alcohol  in  urine  show  that 
the  absorption  must  be  nearly  as  rapid  when  the  solution  is  injected  rectally 
as  when  taken  by  mouth,  so  that  difference  in  rate  of  absorption  can  not  be 
the  cause  for  difference  in  effect,  particularly  on  the  heart-rate.  The  greater 
effect  upon  the  respiratory  quotient  when  levulose  is  ingested  by  mouth  can 
not  be  due  solely  to  absorption,  as  the  rise  in  the  quotient  is  not  proportional 
to  the  amount  ingested.  With  30  grams  in  a  500  c.  c.  solution  given  by 
mouth  in  this  research,  the  rise  in  quotient  was  as  prompt  (see  fig.  91,  p.  159) 
as  with  100  grams  in  a  300  c.  c.  solution  in  the  experiments  of  Benedict  and 
Carpenter.1  In  fact,  the  maximum  increase  (0.17)  over  the  preliminary 
period  with  30  grams  was  nearly  as  great  as  the  maximum  increase  (0.23)  in 
the  100-gram  experiments.  Accordingly,  it  is  not  solely  the  amount  ingested 
which  determines  either  the  rapidity  of  the  rise  or  the  size  of  the  increase  in 
respiratory  quotient. 

Experiments  are  needed  to  determine  the  minimum  quantity  of  levulose 
which  will  produce  an  increase  in  respiratory  quotient.  To  insure  like  rates 
of  absorption,  the  solutions  in  the  mouth  experiments  should  be  given  by  the 
drop  method,  so  as  to  have  the  conditions  of  ingestion  similar  to  those  in 
rectal  feeding. 

The  difference  in  rate  of  absorption  can  not  be  the  cause  for  a  specifically 
different  effect  on  metabolism  when  rectal  injection  takes  place,  for  these  ex¬ 
periments  show  that  levulose,  the  sugar  which  was  more  readily  absorbed, 
had  less,  if  any,  effect  upon  the  respiratory  quotient  than  did  dextrose,  the 
sugar  less  readily  absorbed.  In  other  words,  with  dextrose  and  levulose 
there  is  a  reversed  picture,  so  far  as  the  respiratory  quotient  is  concerned. 
Levulose  produces  the  greater  and  more  positive  effect  when  ingested  by 
mouth,  and  dextrose  is  the  more  effective  in  raising  the  respiratory  quotient 
when  rectally  injected.  The  picture  with  the  rectal  injection  of  levulose  and 
that  with  the  rectal  injection  of  dextrose  thus  differ  specifically,  and  this 
difference  can  not  be  ascribed  to  differences  in  rate  of  absorption  in  rectal  and 
oral  feeding. 

The  idea  that  the  effect  of  rectal  feeding  was  due  to  slowness  of  absorption 
as  compared  with  mouth  feeding  has  been  tested  indirectly  by  other  investi¬ 
gators.  Liithje2  gave  sugar  by  mouth  in  small  portions  at  intervals  through- 

1  Benedict  and  Carpenter:  Carnegie  Inst.  Wash.  Pub.  No.  261,  1918,  p.  242. 

2  Liithje:  Die  Therapie  der  Gegenwart,  1913,  p.  193.  See  p.  12. 


HYPOTHETICAL  DISCUSSION. 


191 


out  the  day  to  diabetics  who  had  shown  complete  urinary  elimination  of 
sugar  when  it  was  given  by  mouth  and  retention  when  it  was  given  rectally. 
In  these  tests  he  found  the  same  difference  in  utilization,  and  came  to  the 
conclusion  that  the  differences  were  not  due  to  slowness  of  absorption. 

Bergmark1  found  different  effects  upon  acidosis,  according  to  whether 
dextrose  was  introduced  by  mouth  or  by  rectum,  but  concluded  that  the 
slowness  of  absorption  with  rectal  injection  was  not  the  cause,  as  he  obtained 
a  definite  lowering  of  the  acidosis  within  2  hours  when  he  gave  six  portions  of 

5  grams  of  dextrose  each  by  mouth,  at  30-minute  intervals. 

The  experiments  by  Jahnson-Blohm2  are  of  interest  in  this  connection  in 
showing  that  small  quantities  of  dextrose  (much  smaller  than  the  quantities 
actually  absorbed  rectally)  increased  definitely  the  blood-sugar.  In  three 
cases  he  gave  6.25  grams  by  mouth  to  a  non-diabetic.  In  one  of  these  exper¬ 
iments,  the  blood-sugar  showed  a  definite  rise  in  15  minutes  and  in  the  other 
two  in  30  minutes.  Staub3  found  that  10  grams  of  dextrose  in  100  c.  c.  of 
water  produced  an  increase  in  the  blood-sugar  of  19  and  21  per  cent  over 
fasting  values.  These  are  mentioned  in  order  to  show  that  definite  metabolic 
changes  can  be  produced  when  small  quantities  of  substances  are  introduced 
by  mouth,  and  that  in  all  probability  the  amounts  and  rate  of  absorption 
rectally  are  large  enough  to  produce  similar  changes  if  the  processes  of  metab¬ 
olism  are  the  same  with  rectal  introduction  as  with  oral  ingestion. 

A  recent  study  by  Gottschalk  and  Nonnenbruch4  on  the  effect  upon  the 
urinary  nitrogen  and  blood  nitrogen  of  ingesting  a  mixture  of  amino-acids 
offers  outside  evidence  on  the  differences  in  metabolism  between  oral  and 
rectal  ingestion.  They  used  “rectamin,”  a  commercial  preparation  of  a 
mixture  of  amino-acids,  designed  for  use  in  rectal  feeding,  and  found  that  the 
ingestion  by  mouth  resulted  in  an  increase  in  the  amino-acid  nitrogen  in  the 
blood,  but  no  increase  in  the  proportion  of  amino-acid  nitrogen  in  the  urine. 
When,  however,  the  material  was  given  rectally,  although  a  much  smaller 
quantity  was  retained,  the  amino-acid  nitrogen  in  the  urine  was  increased 
markedly.  They  conclude  that  when  the  substance  is  absorbed  rectally, 
part  of  it  passes  into  the  systemic  circulation  and  avoids  the  liver.  On 
reaching  the  kidneys  it  is  eliminated.  Gottschalk  and  Nonnenbruch  believe 
that  in  passing  through  the  liver  the  material  is  bound  in  some  way  to  the 
serum  substance,  or  that  it  is  changed  chemically  in  such  a  way  that  it  is 
suitable  for  use  by  the  various  tissues,  but  that  when  such  material  does  not 
pass  through  the  liver,  it  is  treated  as  foreign  matter  and  is  eliminated.  This 
idea  is  in  agreement  with  that  of  Varela  and  Rubino.5 

From  the  evidence  presented  in  this  publication  and  that  from  other 
sources,  it  is  clear  that  there  is  a  specifically  different  metabolism  when  sub¬ 
stances  are  injected  rectally  from  that  when  they  are  introduced  by  mouth. 
The  two  explanations  of  the  effect  of  rectal  feeding,  viz,  avoidance  of  portal 
circulation  and  slowness  of  absorption,  have  been  discussed  in  the  preceding 
pages  to  show  that  some  other  conception  is  necessary  to  fit  the  results  of  our 
experiments.  The  following  hypothesis  is  therefore  offered: 

1  Bergmark:  Skand.  Arch.  f.  Physiol.,  1915,  32,  p.  355. 

2  Jahnson-Blohm:  Upsala  Lakareforenings  Forhandlingar,  1915,  20,  p.  344. 

8  Staub:  Zeitschr.  f.  klin.  Med.,  1921,  91,  p.  44. 

4  Gottschalk  and  Nonnenbruch:  Arch.  f.  exp.  Pathol,  u.  Pharm.,  1923,  99,  pp.  300-314. 

6  Varela  and  Rubino:  Med.  Klinik,  1922,  p.  831. 


192 


HUMAN  METABOLISM  WITH  ENEMATA. 


Hypothesis  Regarding  the  Metabolism  with  Rectal  Feeding. 

The  material  enters  the  rectum  and  colon  and  is  absorbed  both  by  the 
lower  hemorrhoidal  veins  and  by  the  upper  and  middle  hemorrhoidal  veins. 
From  the  two  latter,  the  material  enters  into  the  circulation  by  way  of  the 
portal  system  and  consequently  passes  through  the  liver.  As  the  liver  as 
well  as  the  rest  of  the  alimentary  tract  is  in  a  quiescent  state  at  the  time  that 
absorption  takes  place,  there  is  no  secretion  of  hormones  or  substances  which 
are  elaborated  when  material  is  ingested  by  mouth;  consequently,  the 
metabolism  of  the  substance  introduced  rectally  proceeds  within  the  indi¬ 
vidual  cells  and  tissues  without  the  usual  assistance  and  intercession  of  these 
hormones  and  secretions.  This  presupposes  that  a  sufficient  period  of  time 
has  elapsed  between  the  previous  taking  of  food  by  mouth  and  the  rectal 
injection,  so  that  absorption,  digestion,  and  all  activity  of  the  alimentary 
tract  have  ceased;  otherwise,  the  material  injected  rectally  would  be  utilized 
in  the  same  way  as  when  ingested  by  mouth  with  the  liver  and  the  alimentary 
tract  in  active  operation.  From  this  it  should  not  be  inferred  that  the  chem¬ 
ical  transformation  necessarily  takes  place  in  the  liver  itself,  but  only  that 
the  transformation  takes  place  when  the  liver  is  in  active  condition. 

This  hypothesis  would  imply  that  there  are  two  distinct  types  of  metabo¬ 
lism,  one  with  the  alimentary  tract  in  a  quiet  state,  that  is,  a  metabolism 
which  is  universal  throughout  the  body,  and  the  other  a  metabolism  with  the 
alimentary  tract  in  an  active  state  which  is  superimposed  upon  the  general 
metabolism  throughout  the  body.  Johansson1  has  also  formulated  the  theory 
that  there  may  be  two  independent  metabolisms,  namely,  that  there  is  a 
basal  or  ground  metabolism  which  proceeds  independently  of  any  metabolism 
superimposed  upon  it,  and  that  there  is  the  metabolism  of  ingested  material 
by  means  of  which  such  material  is  either  transformed  or  laid  down  in  depots 
to  form  a  reserve  for  the  basal  metabolism.  In  other  words,  his  idea  is  that 
there  is  (1)  a  fundamental  metabolism  which  proceeds  exactly  in  the  same 
manner,  regardless  of  whether  or  not  material  is  ingested,  and  (2)  that  there 
is  a  metabolism  of  ingested  material  which  is  superimposed  upon  the  basal 
metabolism. 

The  hypothesis  here  presented  would  involve  the  idea  that  there  may  be 
two  different  types  of  metabolism,  one  the  metabolism  when  the  alimentary 
tract  is  in  a  quiescent  state  and  the  other  the  metabolism  when  digestion, 
absorption,  transformation,  and  deposition  are  taking  place.  The  former  is 
similar  to  that  during  muscular  work  and  the  other  that  after  a  meal.  It 
would  appear  that  alcohol  and  dextrose  are  substances  that  can  be  utilized 
without  the  intervention  of  an  active  alimentary  tract. 

There  is  evidence  that  the  liver  forms  a  secretion  after  the  ingestion  of  food 
or  during  its  activity,  also  that  the  liver  is  in  a  more  active  condition  after 
food  ingestion.  Cannon  and  Uridil2  found  that  stimulation  of  the  hepatic 
nerves  caused  an  acceleration  of  the  “denervated  heart  ”  when  the  adrenal 
glands  had  been  removed,  and  that  this  acceleration  was  slight  if  the  animal 
was  fasting  or  in  a  poor  condition  and  much  greater  when  the  animal  was 
digesting  meat. 

Cannon  and  Griffith3  sought  further  light  on  the  nature  of  the  substance 

1  Johansson  and  Hellgren:  Festschrift  fur  Olof  Hammarsten,  1906. 

2  Cannon  and  Uridil:  Am.  Journ.  Physiol.,  1921,  58,  p.  353. 

3  Cannon  and  Griffith:  Am.  Journ.  Physiol.,  1922,  60,  p.  544. 


HYPOTHETICAL  DISCUSSION. 


193 


causing  the  acceleration.  They  found  that  the  accelerator  effect  could  be 
produced  by  reinjecting  into  the  inferior  vena  cava  some  blood  which  had 
been  drawn  from  the  hepatic  veins  during  stimulation.  Feeding  carbohy¬ 
drate  or  fat  was  without  influence,  and  the  stimulation  was  most  effective 
when  milk  or  meat  had  been  fed  and  the  animal  was  digesting  meat.  They 
also  injected  intravenously  amino-acids  on  the  supposition  that  these  might 
have  been  released  by  the  liver  during  stimulation  of  the  hepatic  nerves,  but 
tyrosine  was  the  only  one  causing  an  increased  heart-rate.  Glucose,  urea, 
catalase,  or  bile  caused  no  acceleration  of  the  heart-beat.  They  concluded 
that  a  substance  of  special  and  unknown  nature  is  discharged  into  the  blood¬ 
stream  when  the  hepatic  nerves  are  stimulated. 

Asher1  studied  the  perfused  heart  of  the  frog,  using  blood  that  had  not 
passed  through  the  liver,  and  subsequently  perfused  the  same  heart  with 
blood  which  had  passed  through  the  liver  of  another  frog.  In  the  second 
case  the  heart-beats  were  augmented  in  size  and  in  frequency.  Similar 
experiments  with  tortoise  heart  gave  results  of  like  character.  In  both  series 
the  primary  condition  could  be  restored  by  perfusing  with  a  fluid  which  had 
not  passed  through  the  liver. 

Mann 2  has  recently  studied  the  activity  of  the  liver  and  gall-bladder  in  the 
dog.  He  found  that  the  liver  during  fasting  sometimes  secreted  practically 
no  bile,  but  that  it  was  always  much  more  active  during  digestion.  He  says 
he  has  come  to  regard  the  gall-bladder  “as  a  part  of  a  mechanism  whereby 
the  secretory  activity  of  the  liver  is  correlated  with  that  of  the  gastrointes¬ 
tinal  tract  ”,  and  further,  “  that  the  function  of  the  gall  -bladder  is  to  stimulate 
the  liver  to  increased  activity  at  the  time  the  gastro-intestinal  tract  is  most 
active.”  He  also  states  that  he  is  coming  to  believe  that  the  activity  of  the 
liver  is  associated  with  digestion. 

These  studies  have  been  cited  to  show  that  there  is  evidence  of  and  belief 
in  the  secretory  activity  of  the  liver,  and  that  this  activity  is  greater  during 
digestion. 

The  hypothesis  above  outlined  should  be  susceptible  of  experimental 
proof.  If  the  increase  in  respiratory  quotient  due  to  the  ingestion  of  levulose 
takes  place  when  the  alimentary  tract  is  in  active  condition,  then  it  ought  to 
occur  by  whatever  way  it  is  introduced,  provided  the  alimentary  tract  is 
active.  For  example,  if  protein  is  ingested  by  mouth  and  levulose  by  rectum, 
according  to  the  hypothesis  one  would  expect  the  respiratory  quotient  to 
rise.  One  would  also  expect  the  blood-sugar  in  the  form  of  levulose  to  rise 
after  the  rectal  injection  of  levulose,  provided  it  is  not  immediately  utilized. 
Rubino  and  Varela  found  slightly  greater  increase  in  blood-sugar  with  levu¬ 
lose  than  with  dextrose  after  rectal  injection.  One  condition  should  be  con¬ 
formed  to  in  any  study  of  the  metabolism  of  rectal  feeding,  viz,  that  the  time 
of  making  the  experiment  should  be  long  enough  after  the  last  food  in  order 
to  insure  a  quiescent  state  of  the  alimentary  tract  and  accessory  organs. 
This  was  not  done  in  our  experiments,  and  the  variations  in  the  results  may 
be  due  to  different  conditions  in  the  alimentary  tract. 


1  Asher:  Proc.  Soc.  Exp.  Biol,  and  Med.,  1923-24,  21,  p.  193. 

2  Mann:  Journ.  Am.  Med.  Assoc.,  1924,  83,  p.  829. 


194 


HUMAN  METABOLISM  WITH  ENEMATA. 


SUMMARY. 

The  effect  of  rectal  injection  of  solutions  containing,  respectively,  0.6  per 
cent  of  sodium  chloride,  5,  7.5,  and  10  per  cent  of  ethyl  alcohol,  and  varying 
amounts  of  dextrose  and  levulose  was  studied  with  four  young  medical  stu¬ 
dents  with  special  reference  to  absorption,  the  effect  upon  the  flow  and  com¬ 
position  of  urine,  and  the  respiratory  exchange. 

The  absorption  of  a  5  per  cent  alcohol  solution  was  determined  in  21  ob¬ 
servations  with  4  subjects.  When  the  solution  was  injected  rectally  in 
quantities  varying  from  220  to  1,020  c.  c.  and  with  the  time  of  retention  over 
2|  hours,  the  absorption  was  at  least  98  per  cent.  The  use  of  a  second  wash¬ 
out  in  7  cases  showed  that  the  first  wash-out  removed  practically  all  of 
the  unabsorbed  alcohol. 

The  absorption  of  265  to  810  c.  c.  of  a  7.5  per  cent  alcohol  solution  injected 
by  rectum  was  determined  in  6  cases  with  3  subjects,  and  was  found  to  be  98 
per  cent  or  over  when  the  time  of  retention  was  somewhat  over  an  hour.  A 
second  wash-out  showed  in  all  cases  that  the  first  removed  all  but  extremely 
small  quantities  of  alcohol. 

The  absorption  of  260  to  265  c.  c.  of  a  10  per  cent  alcohol  solution  was  de¬ 
termined  in  4  cases  and  found  to  be  99  per  cent  or  over  when  the  injection 
was  retained  for  2|  hours. 

The  absorption  of  30  grams  of  dextrose  in  500  c.  c.  of  a  0.6  per  cent  sodium- 
chloride  solution  was  determined  in  8  cases  and  in  2  observations  in  which  a  5 
per  cent  alcohol  solution  was  used  as  the  medium.  The  amounts  absorbed 
varied  from  17.5  to  26.3  grams.  The  time  of  retention  ranged  from  2  hours 
and  17  minutes  to  6  hours  and  24  minutes.  The  amounts  of  dextrose  re¬ 
covered  in  the  second  wash-out  varied  from  0  to  3.5  grams.  The  absorption 
from  60  grams  in  1,000  c.  c.  of  a  0.6  per  cent  sodium-chloride  solution  was 
34.6  grams  in  5  hours  and  25  minutes.  The  results  as  a  whole  indicate  that 
the  greater  part  of  the  absorption  takes  place  in  the  first  2  hours,  as  lengthen¬ 
ing  the  time  of  retention  did  not  increase  the  absorption  proportionately. 

The  absorption  of  25  grams  of  levulose  in  500  c.  c.  of  a  0.6  per  cent  sodium- 
chloride  solution  was  determined  in  4  experiments,  of  37.5  grams  of  levulose 
in  750  c.  c.  in  one  experiment,  of  50  grams  in  1,000  c.  c.  in  2  experiments,  and 
of  50  grams  in  500  c.  c.  in  3  experiments.  From  16.2  to  21.8  grams  were  ab¬ 
sorbed  when  25  grams  were  injected  and  from  24.8  to  48.0  grams  when  50 
grams  were  given.  The  time  of  retention  ranged  in  the  whole  series  from  1 
hour  and  29  minutes  to  4  hours  and  35  minutes.  In  4  cases  the  unabsorbed 
solution  was  voided  naturally  and  the  concentration  of  levulose  was  always 
found  to  be  less  than  the  concentration  of  the  injected  solution.  This  indi¬ 
cates  that  either  unabsorbed  material  was  diluted  in  the  intestine  or  else 
that  the  levulose  (solute)  was  absorbed  more  rapidly  than  the  water  (sol¬ 
vent)  .  Sodium  chloride  was  never  found  in  the  wash-outs. 

The  urine  of  the  subjects  was  collected  over  a  period  of  time  beginning 
about  an  hour  before  injection  and  ending  with  the  end  of  the  observation. 
The  concentration  of  alcohol  in  the  urine  was  found  to  vary  from  0  to  0.40 
mg.  per  cubic  centimeter  when  a  5  per  cent  alcohol  solution  was  injected  in 
the  same  quantities  and  with  the  same  times  of  retention  as  in  the  absorption 
experiments  previously  mentioned.  The  proportion  of  the  injected  alcohol 
eliminated  in  the  urine  varied  from  0  to  0.9  per  cent.  With  a  7.5  per  cent 


SUMMARY. 


195 


alcohol  solution  injected  in  the  same  amounts  and  retained  for  the  same  pe¬ 
riods  as  in  the  absorption  experiments,  the  concentration  of  alcohol  in  the 
urine  was  0  to  0.56  mg.  per  cubic  centimeter,  and  the  proportion  eliminated 
from  0  to  1.2  per  cent.  Similarly,  in  the  observations  with  a  10  per  cent 
alcohol  solution,  the  alcohol  per  cubic  centimeter  of  urine  varied  from  0.10  to 
0.33  mg.  and  the  proportion  eliminated  from  0.4  to  0.7  per  cent. 

Six  experiments  were  made  in  which  5,  7.5,  and  10  per  cent  alcohol  solu¬ 
tions  were  given  by  mouth  in  quantities  containing  18.75  to  25  grams.  The 
urine,  collected  in  the  same  manner  as  in  the  rectal  injection  experiments, 
contained  from  0.19  to  0.32  mg.  per  cubic  centimeter  and  the  elimination  of 
alcohol  given  by  this  method  was  from  0.5  to  1.1  per  cent. 

There  were  8  experiments  with  rectal  injection  of  a  5  per  cent  alcohol  solu¬ 
tion  in  quantities  equivalent  to  420  to  750  c.  c.  in  which  the  urines  were  col¬ 
lected  in  as  short  periods  as  possible  (approximately  30  minutes  to  1  hour) 
over  a  period  of  3f  to  6i  hours,  also  one  experiment  with  rectal  injection  of 
250  c.  c.  of  a  10  per  cent  alcohol  solution  under  like  conditions.  The  maxi¬ 
mum  concentration  was  0.35  mg.  per  cubic  centimeter  with  the  5  per  cent 
solution  and  0.36  mg.  per  cubic  centimeter  with  the  10  per  cent  solution. 
The  peak  of  concentration  occurred  within  2  hours  from  the  beginning  of  the 
injection.  When  the  amount  injected  was  500  c.  c.  of  a  5  per  cent  solution 
or  under,  alcohol  was  not  present  in  the  urine  at  the  end  of  5  hours. 

Three  experiments  of  similar  character,  with  500  c.  c.  of  a  5  per  cent  solu¬ 
tion,  and  one  with  250  c.  c.  of  a  10  per  cent  solution,  all  taken  orally,  gave  as  a 
maximum  concentration  0.38  mg.  per  cubic  centimeter,  the  peak  occurring 
within  the  first  2  hours.  In  only  one  experiment  with  a  5  per  cent  solution 
was  the  collection  continued  until  there  was  no  alcohol  in  the  urine,  viz,  5 
hours. 

There  were  four  urines  which  gave  evidence  of  the  presence  of  conjugated 
alcohol. 

The  rectal  injection  of  alcohol  solutions  caused  an  average  increase  in  the 
volume  of  urine  ranging  from  47  to  193  per  cent,  comparing  the  urine  col¬ 
lected  during  the  experimental  period  with  that  before  the  experiment.  (See 
table  20,  p.  73.)  The  nitrogen  elimination  decreased  5  to  19  per  cent,  and  the 
sodium-chloride  elimination  decreased  25  to  81  per  cent. 

The  rectal  injection  of  a  0.6  per  cent  sodium-chloride  solution  increased  the 
volume  of  urine  on  the  average  52  per  cent,  increased  the  nitrogen  elimina¬ 
tion  2  per  cent,  and  decreased  the  sodium-chloride  output  32  per  cent. 

The  rectal  injection  of  30  grams  of  dextrose  in  500  c.  c.  of  a  0.6  per  cent 
sodium-chloride  solution  in  7  experiments  and  in  500  c.  c.  of  a  5  per  cent  alco¬ 
hol  solution  in  2  experiments  caused  an  average  increase  of  73  per  cent  in  the 
volume  of  urine,  an  average  decrease  of  13  per  cent  in  the  nitrogen  elimination, 
and  an  average  decrease  of  9  per  cent  in  the  sodium-chloride  elimination. 

The  rectal  injection  of  25  grams  of  levulose  in  500  c.  c.  of  a  0.6  per  cent 
sodium-chloride  solution  resulted  in  an  average  increase  of  7  per  cent  in  the 
urinary  volume,  an  average  decrease  of  21  per  cent  in  the  nitrogen  elimina¬ 
tion,  and  an  average  decrease  of  58  per  cent  in  the  sodium-chloride  excretion. 
The  rectal  injection  of  37.5  to  50  grams  of  levulose  in  500  to  1,000  c.  c.  of  a 
0.6  per  cent  solution  of  sodium  chloride  caused  an  average  increase  of  15  per 
cent  in  the  volume  of  urine,  an  average  decrease  of  28  per  cent  in  the  nitrogen 


196 


HUMAN  METABOLISM  WITH  ENEMATA. 


elimination,  and  an  average  decrease  of  67  per  cent  in  the  sodium-chloride 
output. 

The  measurement  of  the  respiratory  exchange  by  means  of  the  collection 
and  analysis  of  expired  air  and  the  count  of  the  heart-rate  were  made  before 
and  after  rectal  injection  of  a  0.6  per  cent  sodium-chloride  solution  in  14 
experiments  with  3  subjects.  The  average  heart-rate  was  6  beats  per  minute 
lower,  the  average  oxygen  absorption  per  minute  20  c.  c.  lower,  and  the  aver¬ 
age  respiratory  quotient  unchanged  at  the  end  of  3  hours  after  injection 
began,  as  compared  with  the  40-minute  period  before  injection. 

Four  experiments  of  a  similar  character  were  made  with  one  of  the  sub¬ 
jects  in  which  the  respiratory  exchange  was  measured  by  means  of  a  chamber 
apparatus  connected  with  a  closed  circuit.  The  pulse-rate  remained  prac¬ 
tically  unchanged,  the  carbon  dioxide  and  respiratory  quotient  rose  slightly 
over  a  period  of  6  hours  after  injection,  while  the  oxygen  absorption  rose  less, 
or  not  at  all. 

The  respiratory  exchange  and  heart-rate  were  measured  in  16  experiments 
with  3  subjects  before  and  after  the  rectal  injection  of  220  to  1,020  c.  c.  of  a  5 
per  cent  alcohol  solution.  The  average  heart-rate  showed  an  increase  of  5 
beats  per  minute  at  the  end  of  2J  hours,  as  compared  with  the  minimum 
average  before  injection.  The  average  oxygen  consumption  per  minute  gave 
a  maximum  increase  of  8  c.  c.  per  minute  (3.5  per  cent)  at  the  end  of  If 
hours,  which  did  not  disappear  at  the  end  of  4  hours  after  rectal  injection  be¬ 
gan.  The  average  respiratory  quotient  fell  0.02  by  the  end  of  1  hour  and  re¬ 
mained  lowered  at  least  3  hours. 

The  respiratory  exchange  and  pulse-rate  were  measured  with  3  subjects  in 
8  experiments  in  which  the  collection  of  expired  air  was  made,  and  its  com¬ 
position  determined  before  and  after  the  rectal  injection  of  265  to  810  c.  c.  of 
a  7.5  per  cent  alcohol  solution,  also  in  5  experiments  with  one  subject  in 
which  the  respiratory  exchange  was  determined  by  means  of  a  chamber  and 
closed  circuit  respiration  apparatus  before  and  after  the  rectal  injection  of 
500  c.  c.  of  a  7.5  per  cent  alcohol  solution.  In  the  first  group  there  was  a  rise 
in  the  pulse-rate  from  an  average  of  67  beats  immediately  after  injection  to 
71  beats  If  hours  after  injection,  a  rise  in  the  average  oxygen  absorption  of 
18  c.  c.  (7.5  per  cent)  within  If  hours  after  injection,  and  a  gradual  lowering 
of  the  average  respiratory  quotient  from  0.84  before  injection  to  0.76  at  the 
end  of  4  hours  after  injection.  In  the  group  with  the  chamber  apparatus,  the 
average  pulse-rate  rose  steadily  from  an  average  of  62  beats  in  the  hour  before 
injection  to  73  beats  at  the  end  of  6f  hours  after  injection,  the  average  oxy¬ 
gen  absorption  increased  from  186  to  225  c.  c.  in  the  same  period,  and  the 
respiratory  quotient  fell  from  0.84  to  0.77.  There  was  no  indication  of  a 
return  to  normal  during  this  time. 

Four  experiments  with  rectal  injection  of  265  c.  c.  of  a  10  per  cent  alcohol 
solution  showed  changes  of  the  same  character  as  with  the  5  and  7.5  per  cent 
alcohol  solutions,  but  not  to  so  marked  a  degree. 

In  6  alcohol  experiments  the  pulse-rate  and  respiratory  exchange  were 
determined  after  ingestion  by  mouth;  in  3  experiments  after  400  c.  c.  of  a  5 
per  cent  solution,  in  2  experiments  after  250  c.  c.  of  a  7.5  per  cent  solution,  and 
in  1  experiment  after  250  c.  c.  of  a  10  per  cent  solution.  Immediately  after 
the  ingestion  there  was  a  rise  of  3  beats  per  minute  in  the  average  pulse-rate, 
with  a  fall  of  5  beats  at  the  end  of  2  hours,  followed  by  a  subsequent  rise  of  9 


SUMMARY. 


197 


beats  per  minute.  Oxygen  absorption  decreased  by  10  c.  c.  is  shown  for  2\ 
hours  after  ingestion,  with  a  return  at  the  end  of  4  hours  to  slightly  above  the 
preliminary  value.  There  was  an  immediate  fall  in  the  average  respiratory 
quotient  which  amounted  to  0.05  in  1  hour,  and  the  quotient  did  not  return 
to  normal  in  4  hours. 

The  respiratory  exchange  was  measured  by  the  collection  and  analysis  of 
expired  air  before  and  after  rectal  injection  of  30  grams  of  dextrose  in  500 
c.  c.  of  a  0.6  per  cent  sodium-chloride  solution  in  5  experiments,  in  500  c.  c.  of 
a  5  per  cent  alcohol  solution  in  2  experiments,  and  in  1  experiment  after  rectal 
injection  of  60  grams  of  dextrose  in  1,000  c.  c.  of  a  0.6  per  cent  sodium-chlo¬ 
ride  solution.  The  chamber  and  closed  circuit  method  was  used  in  2  experi¬ 
ments,  with  injection  of  water  or  sodium-chloride  solution.  The  pulse-rate, 
which  was  counted  in  all  of  the  experiments,  showed  a  rise  beginning  lj 
to  2  hours  after  injection  which  amounted  to  about  5  beats  at  the  end  of 
4  hours.  The  average  oxygen  absorption  was  influenced  but  little.  The 
average  respiratory  quotient  rose  from  a  minimum  of  0.81  before  injection 
to  over  0.86  about  2\  hours  after  injection. 

The  respiratory  exchange  was  measured  by  the  collection  and  analysis  of 
expired  air  and  the  pulse-rate  counted  in  10  experiments  with  3  subjects  after 
the  rectal  injection  of  25  to  50  grams  of  levulose  in  500  to  1,000  c.  c.  of  a  0.6 
per  cent  sodium-chloride  solution.  The  pulse-rate  rose  slightly  in  the  first 
lj  hours  after  injection,  with  a  slight  fall  during  the  next  2J  hours.  The 
average  oxygen  absorption  was  very  slightly  increased  within  an  hour  after 
injection.  The  respiratory  quotient  showed  an  increase  of  0.03  at  the  end  of 
2J  hours,  compared  with  the  average  at  the  beginning  of  injection. 

Suggestions  are  given  as  to  lines  of  investigation  needed  to  elaborate 
and  supplement  the  data  already  accumulated. 

A  theoretical  discussion  of  the  utilization  of  alcohol  is  given  as  calculated 
from  the  changes  in  the  concentration  of  alcohol  in  the  urine  and  the  changes 
in  the  respiratory  quotient,  with  the  conclusion  that  25  grams  will  be  utilized 
in  5  hours.  The  calculation  of  the  maximum  theoretical  increase  in  the 
utilization  of  dextrose  is  made  from  the  change  in  the  respiratory  quotient. 
A  theoretical  discussion  of  the  utilization  of  levulose  when  introduced  rectally 
is  likewise  given. 

The  differences  between  mouth  and  rectal  feeding  are  considered  both 
with  reference  to  the  experiments  here  reported  and  to  the  observations  of 
other  investigators.  The  hypothesis  is  proposed  that  substances  injected 
rectally  are  absorbed  both  by  the  rectal  venous  circulation  (systemic)  and 
by  the  colonic  venous  circulation  (tributaries  of  the  portal  system) ,  distrib¬ 
uted  throughout  the  body,  and  metabolized  without  the  aid  or  the  interven¬ 
tion  of  secretions  or  hormones  elaborated  when  the  material  is  ingested  by 
mouth.  This  hypothesis  assumes,  however,  that  the  rectal  injection  is 
carried  out  long  enough  after  the  ingestion  of  food  by  mouth  so  that  the 
alimentary  tract  and  accessory  organs  are  at  rest. 


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